Transport of organic cations across the blood-testis barrier.

Throughout the mammalian spermatogenic pathway, differentiating spermatogenic cells remain in close contact with somatic Sertoli cells, and this has been considered to be essential for the proliferation, differentiation, and survival of spermatogenic cells. It is thought that Sertoli cells form tight junctions to protect developing spermatogenic cells against harmful agents and provide several nutrients for spermatogenesis from the blood stream. Accordingly, Sertoli cells should regulate the movement of various nutritious and xenobiotic compounds by selective membrane transporters. However, the information on membrane transporters in Sertoli cells is limited. In the present study, we characterized the transport systems of organic cations in Sertoli cells. Uptake of [14C]tetraethylammonium (TEA) was measured by primary-cultured rat Sertoli cells. Initial uptake of TEA was concentration dependent, and an Eadie-Hofstee plot indicated the involvement of two saturable transport systems. The apparent Km values of high- and low-affinity components were comparable to those of previously known organic cation transporter (OCT) or organic cation/carnitine transporter (OCTN). In addition, OCT1, OCT3, OCTN1, and OCTN2 were expressed in Sertoli cells. In conclusion, multiple organic cation transporters, OCTs and OCTNs are expressed in Sertoli cells and the cells regulate transport of cationic compounds to protect and/or maintain the spermatogenesis in testis as the blood-testis barrier.

Specificity of basolateral organic cation transport in snake renal proximal tubules.

We examined the specificity of basolateral organic cation transport in isolated snake (Thamnophis spp.) renal proximal tubules by determining the inhibitory effect of a series of n-tetraalkylammonium (n-TAA) compounds (n = 1-5) on the basolateral uptake of [3H]tetraethylammonium (TEA). The inhibitory potency increased with increasing alkyl chain length, with the apparent Michaelis constants for inhibition of TEA uptake ranging from 3.3 mM for tetramethylammonium (TMA) to 1.0 microM for tetrapentylammonium (TPeA). Thus the apparent affinity of the carrier for n-TAA compounds increases with their increasing hydrophobicity. Because previous data suggested that TEA transport across the basolateral membrane may be asymmetrical and that the exit step may be regulated differently from the entry step, we examined the kinetics of [3H]TEA efflux across the basolateral membrane, Efflux, like entry, occurred by a saturable process that could be described adequately by Michaelis-Menten kinetics. However, the concentration of TEA at one-half Jmax (Kt) for efflux (approximately 110 microM) was about six times the Kt for uptake (approximately 18 muM), indicating that the affinity of the carrier for TEA is greater in the uptake direction than in the efflux direction or that there are separate carriers with different affinities for uptake and efflux. In either case, this difference would favor movement of TEA taken up at the basolateral side across the cells and into the lumen over movement back into the peritubular fluid.

Effect of t-butylhydroperoxide on p-aminohippurat uptake in rabbit renal cortical slices.

OBJECTIVES: Oxygen free radical (superoxide radical, hydrogen peroxide, and hydroxyl radicals) have been considered to be responsible for the pathogenesis of ischemia reperfusion injury and toxic chemical injury in a variety of organs including myocardium, brain, intestine and kidneys. In in vitro models using a suspension of rat proximal tubule segments, t-butylhydroperoxide(t-BHP), a potent oxidant, induces the severity of tubular dysfunction as reflected by decreases in tubular respiration which is associated with a progressive increase in lipid peroxidation. The precise mechanism of t-BHP-induced cell injury remains to be determine. The study was carried out to determine the effect of oxygen free radicals on organic anion transport in renal proximal tubule. METHODS: By renal cortical slices, we studied accumulation of organic ions, PAH efflux oxygen consumption, lactate dehydrogenase (LDH), lipid peroxidation. The data are expressed as the mean +/- SE and evaluated for significance using Student's t-test. A probability level of 0.05 was used to establish significance. RESULTS: Effect of t-butylhydroperioxide(t-BHP), a potent oxidant, on organic anion p-amminohippurate(PAH) uptake was studied in rabbit renal cortical slices. t-BHP inhibited irreversibly PAH and organic cation tetraethylammonium(TEA) uptake in a dose dependent manner with IC50 of approximately 1.0 and 0.85 mM, respectively. The efflux rate constant pf PAH was not altered by the presence of 1 mM t-BHP, indicating that the inhibitory effect of t-BHP on the steady-state accumulation of PAH is due primary to the reduction in the influx of PAH across the basolateral membrane. The kinetic analysis showed that 1mM t-BHP caused a significant reduction in the maximum rate of PAH influx(Vmax) from 1.54 +/- 0.74 to 0.72 +/- 0.54 umol/g/10 min without an effect on Km, indicating that t-BHP depressed PAH influx across the basolateral membrane by reducing the number or turnover rate of active carrier for PAH transport, but not by altering substrate affinity of the carrier. Ouabain-sensitive and -insensitive oxygen consumption was not different between the control and t-BHP-treated slices. t-BHP caused an increase in LDH release and lipid peroxidation in a dose-dependent manner, which were highly correlated with changes in PAH uptake. CONCLUSION: These results suggest that t-BHP inhibition of PAH uptake is attributed to renal tubular cell damage and lipid peroxidation plays an important role in the inhibitory effect of t-BHP on PAH transport in rabbit proximl tubules.

ATP-dependent transport of tetraethylammonium by endosomes isolated from rat renal cortex.

During renal organic cation secretion by some species, intracellular concentrations greatly exceed the 10- to 15-fold ratio predicted by the potential-driven mechanism thought to mediate their basolateral uptake. Free cytoplasmic organic cation concentrations within the tubular cells might be decreased through sequestration within intracellular organelles. The data reported here show that endosomal vesicles isolated from rat renal cortex take up tetraethylammonium (TEA) by an ATP-dependent mechanism. Addition of 0.2-5 mM ATP to the medium stimulated uptake 5- to 10-fold at 5 min and 20-fold at 60 min. More than 80% of the ATP-dependent uptake was associated with an osmotically active space. The nonhydrolyzable ATP analogue, adenosine 5'-O-(3-thiotriphosphate), did not stimulate TEA uptake. Mg2+ and Cl- were required for stimulation. Uptake was inhibited by several organic cations, including TEA itself. Uptake was also inhibited by inhibitors of intravesicular acidification, e.g., monensin and N-ethylmaleimide. Furthermore, the ATP requirement could be bypassed by establishing a pH gradient (inside acidic). These data show that endosomal TEA accumulation is mediated by proton/TEA exchange and is driven by the pH gradient maintained by H(+)-adenosinetriphosphatase. This potent sequestration mechanism may play an important role in organic cation secretion.

Peritubular organic cation transport in isolated rabbit proximal tubules.

The physiological characteristics of peritubular organic cation transport were examined by measuring the transport of the organic cation tetraethylammonium (TEA) in rabbit renal proximal tubule suspensions and isolated nonperfused rabbit renal proximal tubules. Peritubular organic cation transport in both single S2 segments and suspensions of isolated renal proximal tubules was found to be a high-capacity, high-affinity, carrier-mediated process. For tubule suspensions, the maximal capacity of the carrier for TEA (Jmax) and the concentration of TEA at 1/2 Jmax (Kt) (1.49 +/- 0.21 nmol.min-1.mg dry wt-1 and 131 +/- 16 microM, respectively), did not differ significantly from those measured in single S2 segments (Jmax, 1.16 +/- 0.075 nmol.min-1.mg dry wt-1; Kt, 108 +/- 10 microM). In addition, the pattern of inhibition of peritubular TEA transport by long-chain n-tetraalkylammonium compounds (n = 1-5) was both qualitatively and quantitatively similar in single S2 segments and tubule suspensions, exhibiting an increase in inhibitory potency with increasing alkyl chain length. For example, in tubule suspensions, apparent Michaelis constants for inhibition of TEA uptake ranged from 1.3 mM for tetramethylammonium (TMA) to 0.8 microM for tetrapentylammonium (TPeA). To determine whether these compounds were substrates for the peritubular organic cation transporter, their effect on the efflux of [14C]TEA from tubule suspensions was examined. A concentration of 0.5 mM of the short-chain tetraalkyls TMA or TEA increased the efflux of [14C]TEA (i.e., trans-stimulated) from tubules in suspension. The longer-chain tetraalkyls tetrapropylammonium, tetrabutylammonium, and TPeA all decreased the efflux of [14C]TEA from tubules in suspension; TPeA completely blocked efflux.(ABSTRACT TRUNCATED AT 250 WORDS)

Ethanol inhibits tetraethylammonium chloride-induced synaptic plasticity in area CA1 of rat hippocampus.

Dendritic recordings of the rat hippocampal formation were used to assess the ability of ethanol to inhibit the induction of synaptic plasticity due to bath application of the K+ channel blocker, tetraethylammonium chloride (TEA). Brief application of TEA resulted in the enhancement of the population excitatory postsynaptic potential (EPSP) slope by an average of 26 +/- 3% over the pre-TEA baseline. However, coapplication of TEA and ethanol (100 mM) resulted in enhancement of only 10 +/- 2% of the EPSP slope. These data suggest that LTP (long-term potentiation) due to the activation of voltage-gated Ca2+ channels is also inhibited by ethanol.

1,1'-diethyl-2,2'-cyanine (decynium22) potently inhibits the renal transport of organic cations.

The excretion of cationic compounds by renal proximal tubule cells involves at least two distinct transporters: the basolateral type which transports organic cations from the plasma into the proximal tubule cell, and the apical type which secretes the organic cations into the lumen of the tubule. However, potent inhibitors were known for neither type of transporter. Here we introduce a compound, decynium22, that potently, competitively, and selectively inhibits the apical type of the renal organic cation transporter. The transport of the prototypical organic cation 14C-tetraethylammonium through the apical plasma membrane of clonal proximal tubule cells (LLC-PK1) was used as experimental system. Initial rates of 14C-tetraethylammonium transport into LLC-PK1 cells were saturable, the Km and Vmax being 27 mumol/l and 200 pmol/(mg protein.min), respectively. Decynium22 competitively and potently inhibited 14C-tetraethylammonium transport (Ki = 5.6 nmol/l). Moreover, the effect of decynium22 on basolateral to apical directed transepithelial transport of 14C-tetraethylammonium through a confluent monolayer of LLC-PK1 cells was determined. Decynium22 (30 nmol/l) applied to the apical medium, reduced transepithelial transport by 76% and increased intracellular accumulation of 14C-tetraethylammonium 1.5-fold. In contrast, application of 30 nmol/l decynium22 to the basolateral medium failed to affect transepithelial transport and intracellular accumulation of 14C-tetraethylammonium. Decynium22 is the most potent inhibitor of the renal transport of organic cations known so far. With decynium22 it is now possible to distinguish precisely between a decynium22-sensitive apical type and a decynium22-resistant basolateral type of renal organic cation transporter in renal proximal tubule cells.

Organic cation transport by rat hepatocyte basolateral membrane vesicles.

Hepatocyte basolateral membrane possesses transport systems for mediated uptake of organic cations, the first step in the subsequent biliary excretion and/or metabolism of these compounds. The purpose of these studies was to evaluate potential mechanisms for transport of this class of solutes across this membrane by measuring 3H-labeled tetraethylammonium ([3H]TEA) transport into rat hepatocyte basolateral membrane vesicles. [3H]TEA uptake was stimulated by an outwardly directed proton gradient consistent with TEA-proton exchange. Proton gradient-stimulated [3H]TEA uptake was inhibited by quinidine and by the combination of valinomycin and carbonyl cyanide m-chlorophenylhydrazone (CCCP) but not by CCCP alone or by N1-methylnicotinamide (NMN). An outwardly directed TEA gradient also stimulated uptake of [3H]TEA with values at early time points exceeding those at equilibrium. This trans-stimulation or countertransport was saturable with an apparent Michaelis constant of 106 microM and maximal velocity of 434 pmol.mg-1.15 s-1. TEA countertransport was cis-inhibited by quinidine, cimetidine, and thiamine and by low temperature, but not by NMN. Thiamine was also capable of trans-stimulating [3H]TEA uptake. An outwardly directed potassium gradient enhanced and an inwardly directed potassium gradient reduced TEA countertransport but had no effect on [3H]TEA uptake occurring in the absence of other electrochemical driving forces. These studies indicate that there are at least two potential mechanisms in the hepatocyte basolateral membrane for transport of organic cations; organic cation-organic cation exchange (countertransport) and organic cation-proton exchange. Furthermore, the results are consistent with the existence of more than one transporter with different substrate affinities in each of these categories.(ABSTRACT TRUNCATED AT 250 WORDS)

Biphasic effect of tetraethylammonium on canine purkinje fibre action potential configuration.

1. Using conventional microelectrode techniques a biphasic effect of tetraethylammonium (5 mmol/l) on the configuration of action potentials recorded from isolated canine Purkinje fibres: action potentials were first shortened (early effect) and then lengthened (late effect) by tetraethylammonium. 2. The early effect of tetraethylammonium also included lengthening of phase 1 duration and elevation of the plateau amplitude. These early effects reached steady-state within the first 3 min of superfusion and were readily reversed within 3 min of initiating washout of the drug. 3. The late effect (gradual lengthening of repolarisation during phase 3) failed to reach steady-state within the initial 60 min of superfusion and was not reversible. 4. The early effects of tetraethylammonium were more marked at slow driving rates and were not affected by blockade of alpha- and beta-adrenoceptors using 1 mumol/l phentolamine and 1 mumol/l propranolol. 5. The early effects of tetraethylammonium were mimicked by 4-aminopyridine (0.5 mmol/l), and in the presence of 4-aminopyridine tetraethylammonium failed to induce further changes in action potential morphology. 6. The early effects of tetraethylammonium may be due to inhibition of the transient outward current. 7. The rapid onset and reversibility of these early effects suggest that tetraethylammonium may act from outside the cell membrane.

Repulsion between tetraethylammonium ions in cloned voltage-gated potassium channels.

Tetraethylammonium ion (TEA+) blocks voltage-gated K+ channels by acting at two sites located at opposite ends of the aqueous pore. This allowed us to test two predictions made by models of ion permeation, namely that K+ channels can be simultaneously occupied by multiple ions and that the ions repel each other. We show that externally applied TEA+ antagonize block by internal TEA+ and vice versa. The antagonism is less than predicted for competitive binding, hence TEA+ may occupy both sites simultaneously. External TEA+ and internal TEA+ reduce each others affinity 4- to 5-fold. In addition, K+ antagonizes block by TEA+ at the opposite side of the membrane, and external TEA+ antagonizes is block by internal Ba2+. The antagonism between ions applied at opposite sides of the membrane may be common to all cations binding to K+ channels.

A Ca(2+)-dependent K+ current is enhanced in arterial membranes of hypertensive rats.

This study was designed to investigate the role and regulation of arterial membrane K+ channels in hypertension. Aortic segments from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were suspended for isometric tension recording. In other experiments, proximal aortic segments (PS) (exposed to high pressure) and distal aortic segments (DS) (exposed to lower pressure) were removed from surgically coarcted Sprague-Dawley rats and similarly prepared. Aortas from SHR and PS dose-dependently contracted to the K+ channel blocker tetraethylammonium (TEA) (0.1-10 mM), and this contraction was abolished by preincubation with 0.1 microM nifedipine. In contrast, the same concentrations of TEA did not contract either WKY or DS aortas. Since block of K+ channels by TEA had a different effect on aortic segments exposed to high versus low blood pressure, we compared whole-cell K+ currents in isolated vascular cells from the same aortas. The reversal potentials of depolarization-induced outward currents in WKY, SHR, DS, and PS aortic cells showed a Nernst relation to external K+ concentration indicative of selective K+ permeability. TEA (1 and 10 mM) was equipotent in blocking these K+ currents in patch-clamped cells from all aortic preparations, suggesting that the lack of TEA-induced contractions in WKY and DS aortas was not due to an absence of TEA-sensitive K+ channels in these arterial membranes. However, when the Ca2+ ionophore A23187 (10 microM) was used to increase the level of cytosolic Ca2+ in patch-clamped cells, the K+ current density in SHR and PS aortic cells was twofold or more higher than in WKY and DS cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation of intracellular calcium by potassium channel openers in vascular muscle.

We investigated two putative K+ channel openers, pinacidil and BRL34915 (cromakalim), and demonstrated their vasorelaxant effectiveness on rat artery contractions induced by K+, tetraethylammonium (TEA), or norepinephrine. The K+ channel opener-induced decrease in tension was rapid, even when tension was stimulated by 100 mmol/l K+. Measurements of intracellular free Ca++ (activity) by ultra-high sensitivity digital imaging microscopy was carried out by briefly loaded fura 2 (fluorescence ratio) quantitation in isolated, contracting cells of rat azygos vein. Submicron resolution was achieved by measuring cytoplasmic Ca(++)-sensitive fluorescence at each pixel, and size and intensity of areas with high Ca++ concentrations, called hot spots, were determined by a computer-generated, 3 lambda algorithm. Hot spots, which most likely represent the sites of Ca++ release and re-uptake by Ca(++)-regulatory organelles, increased in size and intensity upon addition of K+ or norepinephrine, reaching an early peak prior to the whole cell average peak in cytoplasmic Ca++ activity. Both norepinephrine and K(+)-induced stimulation resulted in Ca++ activity increases that were primarily due to Ca++ release from storage sites. Reduction of free Ca++ activity to resting or lower levels occurred upon addition of pinacidil or cromakalim. Intracellular Ca++ decreases due to K+ channel openers appeared abruptly beginning at the central portions of the cells, resulting in a pronounced early drop in central Ca++ activity while elevated Ca++ levels persisted at the periphery. While this late stage residual of peripheral Ca++ appears to be a significant step in the vascular muscle relaxant action of both K+ channel opener drugs, the level of Ca++ at peripheral sites was greater in response to pinacidil than to cromakalim. The results of this study suggest that in addition to increasing K+ conductance, pinacidil and cromakalim cause 1) decreased Ca++ activity in central regions of the myocytes, and 2) a shift in Ca++ distribution to primarily subsarcolemmal sites. These observations lead us to hypothesize separate control of peripheral and central Ca++ activity within a vascular muscle cell, with Ca++ redistribution that can be altered by vasorelaxants. We suggest that intracellular Ca++ redistribution may contribute the membrane potential-independent part of the vasorelaxant action of the K+ channel openers.

Transport of tetraethylammonium by a kidney epithelial cell line (LLC-PK1).

We investigated whether the LLC-PK1 epithelial cell line (which shows many characteristics of proximal tubular cells) also is capable of transporting an organic ion. Suspended LLC-PK1 cells accumulated tetraethylammonium (TEA). The uptake showed characteristics of a facilitated mechanism; TEA uptake was saturable and temperature-dependent and was inhibited by other organic cations. Quinine and mepiperphenidol were the most potent inhibitors, whereas N1-methylnicotinamide and morphine inhibited the transport system only slightly at doses of 10(-3) M. Basolateral-to-apical TEA flux through LLC-PK1 monolayers was five to six times larger than that of mannitol, a nontransported compound, whereas apical-to-basolateral TEA and mannitol fluxes were equal. Only the basolateral-to-apical TEA flux was inhibited by quinine. Under similar experimental conditions, no transport of p-aminohippuric acid was observed. It is concluded that LLC-PK1 cells are able to transport TEA, as do cells of the proximal tubule.

Tetraethylammonium induced coronary spasm in isolated perfused rabbit heart: a hypothesis for the mechanism of coronary spasm.

The vasoactive effect of tetraethylammonium, which is known to reduce potassium conductance of the membrane of arterial smooth muscle cells, was tested on large epicardial coronary arteries in isolated perfused rabbit hearts. These hearts were perfused selectively through the right and left coronary arteries. Left coronary angiography was performed using Krebs-Henseleit solution containing phenolsulfonphthalein under constant pressure, and the epicardial electrogram was recorded. In 59 of 114 hearts 30 mmol.litre-1 tetraethylammonium induced severe constriction of the left epicardial coronary artery, which was associated with electrocardiographic ST segment elevation in some cases. The induced spasm was prevented by diltiazem (200 nmol.litre-1), glyceryl trinitrate (2 mumol.litre-1), or nicorandil (10 mumol.litre-1), but not by phentolamine (1 mumol.litre-1) or atropine (1 mumol.litre-1). In hearts in which tetraethylammonium did not induce spasm, subsequent addition of ergonovine (100 nmol.litre-1) or alkalinisation of the perfusate (pH 7.65-7.70) provoked spasm. The tetraethylammonium induced spasm resembled the coronary spasm seen in patients with variant angina and was a reproducible in vitro model of coronary spasm. These observations support the hypothesis that the primary defect in patients with coronary spasm is decreased potassium permeability of the membrane of coronary arterial smooth muscle cells.

8-Bromo-cyclic GMP abolishes TEA-induced slow action potentials in canine trachealis muscle.

Using intracellular microelectrodes, we investigated whether 8-bromo-guanosine 3':5'-cyclic monophosphate (cGMP) influenced the electromechanical effects of tetraethylammonium (TEA) on canine tracheal smooth muscle. We found that 20 mM TEA depolarized airway smooth muscle cells from -58 +/- 3 mV (means +/- S.D.) to -44 +/- 2 mV and caused spontaneous action potentials (APs) to develop which were 31 +/- 2 mV in amplitude. These APs, and the phasic contractions electrically coupled to them, were totally abolished in buffer containing 0.1 mM cGMP. Our findings suggest that cGMP markedly affects the channels mediating TEA-induced APs in airway smooth muscle.

Effects of diltiazem on electrical responses evoked spontaneously or by electrical stimulation in the antrum smooth muscle cells of the guinea-pig stomach.

In circular smooth muscle cells of the guinea-pig stomach (antrum), diltiazem (10(-6)-10(-5)M) blocked the overshooting spike potential generated either spontaneously or by electrical stimulation in the presence of 2 mM tetraethylammonium chloride, but did not block the slow wave and the abortive spike potential. The membrane was depolarized by high concentrations of diltiazem (more than 3 X 10(-6)M), and this depolarization was associated with an increase in the membrane resistance. The interval between slow waves was shortened to about 0.90 times the control (14.7s) by 10(-5)M diltiazem. Transmural nerve stimulation evoked an inhibitory junction potential (i.j.p.) and enhanced the subsequently generated slow wave. Tetrodotoxin (3 X 10(-7)M) blocked both responses but atropine (10(-6)M) blocked only the latter. Diltiazem (more than 10(-6)M) increased the amplitude of the i.j.p. and depressed the enhancement of the slow wave produced by transmural nerve stimulation, presumably due to depolarization of the membrane. The latency for the i.j.p. remained the same in the presence of diltiazem (10(-5)M). It is concluded that in the guinea-pig stomach, diltiazem blocks Ca-influx during the generation of the overshooting spike potential, but not the Ca-influx related to generation of the abortive spike potential or the slow wave. The cholinergic excitatory and the non-adrenergic, non-cholinergic inhibitory transmission may not be much affected by diltiazem.

The action of intravenous anaesthetic and central depressant drugs on the contractures elicited by tetraethylammonium in the chick biventer cervicis muscle.

A group of intravenous anaesthetic drugs was compared with methohexitone sodium for their ability to potentiate tetraethylammonium induced contractures of the chick biventer cervicis muscle (TEA test). The equipotent concentrations in the TEA test were: methohexitone 8.8 X 10(-5) M, propanidid 1.78 X 10(-4) M, althesin 3.58 X 10(-5) M (in terms of alphaxalone), etomidate 1.6 X 10(-4) M, thiopentone 2.13 X 10(-5) M and valium 4.95 X 10(-5) M. There was no relation between activity in the TEA test and excitatory muscular activity reported clinically. The central depressant drugs ethyl alcohol and urethane also potentiated TEA but they were only active in high concentrations (10(-1) - 10(-2) M). alpha-Chloralose was inactive but paraldehyde (3.8 X 10(-3) M) actually reduced TEA induced contractures. Lipophilicity is only one factor in determining activity in the TEA test, the ability to block Ca2+ reuptake may also be important.

The neuromuscular effects of lignocaine.

The local anesthetic drug lignocaine, in concentrations which completely block both nerve and muscle action potentials, produces concentration-dependent contractures in the vertebrate skeletal and smooth muscle fibres. The contractures produced by lignocaine were not related to membrane depolarization. Although lignocaine greatly reduced the depolarizations and contractures produced by depolarizing agents, such ACh or carbachol, it had a differential effect on the responses produced by tetraethylammonium (TEA) at the chick neuromuscular junction. Lignocaine reduced the TEA-induced depolarizations while it markedly enhanced the contracture responses. In the absence of membrane depolarization, the contractures produced by lignocaine may be attributed to an effect on release of intracellular calcium (Ca2+) from the sarcoplasmic reticulum (SR). The results suggested a multiple site of action of lignocaine at the vertebrate neuromuscular junction.

[Effect of tetraethylammonium on electrophysiologic properties of pulmonary artery smooth muscle cells]. / Vliianie tetraétilammoniia na élektrofiziologicheskie svoístva gladkomyshechnykh kletok legochnoí arterii

Using the microelectrode technique combined with sucrose gap method it was shown that in the tetraethylammonium (TEA) solution a pulmonalis muscle cells exhibited spontaneous or elicited action potentials caused by depolarizing current. It is suggested that the appearance of the electrical activity due to inhibition with TEA of the voltage-dependent delayed potassium current, early activation of which in normal Krebs solution prevented the action potential development. Ca ions took part in the action potential generation because it was inhibited by Mn ions. Besides, delayed potassium current inhibition, TEA showed nonspecific action on the arterial muscle cells expressed in the following: 1) depolarizing action accompanied by increase of the membrane resistance; 2) stimulation of the extracellular calcium entry into the muscle cells followed by tonic muscle contraction; 3) establishment of coupling between the contraction and the resting potential.