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2.
Neurophysiol Clin ; 42(5): 267-80, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23040698

RESUMEN

Laser-evoked potentials are the most extensively validated method to objectively assess nociceptive pathway function in humans. Here, we review merits and shortcomings of alternative techniques using different principles of stimulus generation to stimulate Aδ- or C-fibers. Fast ramp contact heat stimuli yield reproducible responses; however, stimulus location needs to be changed to reduce peripheral habituation, and the limited steepness of temperature ramps may result in response jitter and absence of averaged responses even in some healthy subjects. Inverse temperature ramps can serve to evoke cool evoked potentials to specifically test the cold pathway; the clinical impact of such findings is promising but uncertain to date, and availability of devices optimized for this purpose is currently limited. Mechanical stimuli excite low- or high-threshold mechanoreceptors depending on both the probe surface and the applied force. Electrical stimuli can be used to excite nerve fibers directly in the epidermis, the mucosa of the gut, or the tooth pulp. Principle limitation of the applicability of mechanical and electrical stimuli is the inevitable co-excitation of tactile (Aß-) fibers. The nasal mucosa can be stimulated using pulsed-CO(2) air streams, which excite chemo-nociceptors; although these stimuli are specific to excite thin trigeminal afferents, their use is limited as it is restricted to a relatively small region. Current data do not allow a comparative analysis on their respective diagnostic values. Quantification of analgesic efficacy in healthy subjects has been established and may be useful in phase I and IIa clinical trials.


Asunto(s)
Potenciales de Acción/fisiología , Potenciales Evocados/fisiología , Fibras Nerviosas/fisiología , Piel/inervación , Animales , Humanos , Rayos Láser , Estimulación Física
3.
Acta Psychiatr Scand ; 120(1): 62-70, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19133877

RESUMEN

OBJECTIVE: Several studies have shown reduced pain perception in patients with borderline personality disorder (BPD) and current self-injurious behavior (SIB). The aim of the present study was to test whether pain perception in patients with current SIB is different from that of patients who had stopped SIB, and whether pain perception of the latter group differs from healthy controls (HC). METHOD: We investigated 24 borderline patients and 24 HC. Thirteen patients showed current SIB (BPD-SIB) and 11 patients did not exhibit SIB anymore (BPD-non-SIB). Pain thresholds were assessed using thermal stimuli and laser radiant heat pulses. RESULTS: We found significant linear trends for all pain measures. The BPD-SIB group was less sensitive than the BPD-non-SIB group and the latter were less sensitive than HC. The pain sensitivity negatively correlated with borderline symptom severity. CONCLUSION: The results suggest an association between the termination of SIB, decline of psychopathology and normalization of pain perception in borderline patients.


Asunto(s)
Trastorno de Personalidad Limítrofe/terapia , Umbral del Dolor , Conducta Autodestructiva/psicología , Adulto , Atención , Trastorno de Personalidad Limítrofe/diagnóstico , Trastorno de Personalidad Limítrofe/psicología , Estudios de Casos y Controles , Comorbilidad , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Dimensión del Dolor , Inventario de Personalidad , Psicoterapia , Sensación Térmica , Adulto Joven
4.
Neuroscience ; 143(1): 253-63, 2006 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-16973292

RESUMEN

A subgroup of dorsal root ganglion (DRG) neurons responds to noxious heat with an influx of cations carried by specific ion channels such as the transient receptor potential channel of the vanilloid receptor type, subtype 1 (TRPV1). Application of capsaicin induces a reversible facilitation of these currents. This facilitation could be an interaction of two agonists at their common receptor or be caused by an influx of calcium ions into the cell. Calcium influx into the cell can activate protein kinases such as the extracellular signal-related protein kinase (ERK) pathway. This study explored the kinetics, calcium-dependency and intracellular signals following application of capsaicin and leading to facilitation of heat-induced currents (Iheat) in rat DRG neurons. Application of 0.5 microM capsaicin caused a 2.65-fold increase of Iheat within 2 s, which was significantly correlated to a small capsaicin-induced current. Intracellular application of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), a fast calcium chelator, did not change capsaicin-induced currents or Iheat itself, but inhibited facilitation of Iheat by capsaicin. ERK is activated by calcium influx and membrane depolarization via the mitogen-activated protein kinase/extracellular signal-related protein kinase kinase (MEK). Application of the MEK inhibitor U0126 also inhibited facilitation of Iheat by capsaicin. We conclude that the MEK/ERK cascade is an intracellular signaling pathway playing a vital role in the regulation of nociceptive neurons' sensitivity. The very fast kinetics (less than two seconds) are only explainable with a membrane-attached or at least membrane-near localization of these kinases.


Asunto(s)
Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Ganglios Espinales/citología , Calor , Neuronas/efectos de la radiación , Análisis de Varianza , Animales , Butadienos/farmacología , Calcio/metabolismo , Capsaicina/farmacología , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Inhibidores Enzimáticos/farmacología , Femenino , Masculino , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Potenciales de la Membrana/efectos de la radiación , Neuronas/fisiología , Nitrilos/farmacología , Técnicas de Placa-Clamp/métodos , Fosforilación , Ratas , Ratas Sprague-Dawley , Estadística como Asunto
5.
Neuroscience ; 142(2): 527-39, 2006 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-16889902

RESUMEN

Potassium channels contribute to basic neuronal excitability and modulation. Here, we examined expression patterns of the voltage-gated potassium channel Kv1.4, the nociceptive transduction channels TRPV1 and TRPV2 as well as the putative anti-nociceptive cannabinoid receptor CB1 by immunofluorescence double-labelings in sections of rat dorsal root ganglia (DRGs). Kv1.4, TRPV1 and CB1 were each detected in about one third of neurons (35.7+/-0.5%, 29.4+/-1.1% and 36.4+/-0.5%, respectively, mean diameter 19.1+/-0.3 microm). TRPV2 was present in 4.4+/-0.4% of all neurons that were significantly larger in diameter (27.4+/-0.7 microm; P < 0.001). Antibody double-labeling revealed that the majority of Kv1.4-positive neurons co-expressed TRPV1 (73.9+/-1.5%) whereas none expressed TRPV2. The largest overlap was found with CB1 (93.1+/-0.1%). CB1 expression resembled that seen for Kv1.4 since the majority of neurons expressing CB1-protein also expressed TRPV1 (69.4+/-6.5%) but not TRPV2 (0.6+/-0.3%). When CB1-mRNA was detected using in situ hybridizations an additional subset of larger neurons was labeled including 82.4+/-17.7% of the TRPV2 expressing neurons. However, co-localization of Kv1.4 with CB1-mRNA (92%, mean diameter: 18.5 microm) was essentially the same as with CB1-protein. The almost complete overlap of CB1 and Kv1.4 in nociceptive DRG neurons suggests a functional synergistic action between Kv1.4 and CB1. The potassium channel may have two important roles in nociception. As the molecular basis of A-type current it could be involved in the control of repetitive discharges at peripheral terminals and as a downstream signal transduction site of CB1 in the control of presynaptic transmitter release at central terminals.


Asunto(s)
Ganglios Espinales/citología , Neuronas/metabolismo , Receptor Cannabinoide CB1/metabolismo , Canales de Potasio Shal/metabolismo , Canales Catiónicos TRPV/metabolismo , Animales , Western Blotting/métodos , Recuento de Células/métodos , Células Cultivadas , Inmunohistoquímica/métodos , Hibridación in Situ/métodos , Ratas , Ratas Sprague-Dawley
6.
Schmerz ; 20(3): 219-25, 2006 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-16151753

RESUMEN

The capsaicin receptor TRPV1, once discovered as a receptor for pungent spices, is a polymodal sensor molecule for painful chemical and thermal stimuli. However, TRPV1 plays an important role not only for the integration of acute painful stimuli but also in the genesis of inflammatory processes. The persistent functional sensitization of TRPV1 as well as an up-regulation of its expression may contribute to the development and maintenance of chronic pain states. Thus, TRPV1 is an excellent target for a rational pharmacological treatment of pain. Several additional physiological and pathophysiological functions of TRPV1 are assumed beyond nociception and pain. Activation of TRPV1 seems to contribute to the etiology and pathogenesis of inflammatory diseases concerning, e.g., the gastrointestinal tract, the bladder, and the respiratory system. Therefore, the therapeutic potential of a pharmacological manipulation of TRPV1 may not be restricted to a symptomatic therapy of pain.


Asunto(s)
Nociceptores/fisiopatología , Dolor/fisiopatología , Transducción de Señal/fisiología , Canales Catiónicos TRPV/fisiología , Células Quimiorreceptoras/fisiopatología , Enfermedad Crónica , Humanos , Inflamación/fisiopatología , Umbral del Dolor/fisiología , Sensación Térmica/fisiología , Regulación hacia Arriba/fisiología
7.
J Neuroendocrinol ; 16(7): 577-88, 2004 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15214861

RESUMEN

The contribution of Ca(2+)-activated K(+) channels to hyperpolarizing after-potentials (HAP) of action potentials, to spike-frequency adaptation and thus to the shaping of discharge pattern, was examined in rat supraoptic magnocellular neurosecretory cells. In addition, the expression of BK channels and SK3 subunits of SK channels was studied using double immunofluorescence detection. The presence of BK channels and SK3 subunits was detected in many supraoptic neurones containing either vasopressin or oxytocin. Current-clamp recordings of current-induced spike trains revealed that HAPs comprise a fast and a slow HAP (fHAP and sHAP). Correlation analyses revealed that the increase of the fHAP in amplitude and spike broadening were correlated to a moderate gradual increase of the interspike interval and thus to weak spike-frequency adaptation. By contrast, marked prolongation of the interspike interval and strong spike-frequency adaptation depended on the appearance and on the amplitude of the sHAP. The sHAP and spike-frequency adaptation were blocked by cadmium, as well as by the SK channel antagonist apamin. The fHAP was attenuated by the BK channel antagonist iberiotoxin (IbTX), by the BK/IK channel antagonist charybdotoxin (ChTX) and by apamin. ChTX attenuated fHAPs throughout the entire spike train. By contrast, the IbTX-induced attenuation of the fHAP was restricted to the initial part of the spike train, while the apamin-induced attenuation slowly increased with the progression of the spike train. These results suggest that strong spike-frequency adaptation in supraoptic neurones essentially depends on the generation of the sHAP by activation of SK channels. Comparison of effects of IbTX, ChTX and apamin suggests a complementary contribution of SK-, BK- and IK-channels to fHAPs.


Asunto(s)
Potenciales de Acción/fisiología , Neuronas/fisiología , Canales de Potasio Calcio-Activados/fisiología , Núcleo Supraóptico/fisiología , Potenciales de Acción/efectos de los fármacos , Adaptación Fisiológica , Animales , Apamina/farmacología , Caribdotoxina/farmacología , Técnica del Anticuerpo Fluorescente , Masculino , Neuronas/citología , Neuronas/efectos de los fármacos , Sistemas Neurosecretores/citología , Sistemas Neurosecretores/fisiología , Neurotoxinas/farmacología , Oxitocina/metabolismo , Péptidos/farmacología , Canales de Potasio Calcio-Activados/efectos de los fármacos , Subunidades de Proteína/efectos de los fármacos , Subunidades de Proteína/fisiología , Ratas , Ratas Sprague-Dawley , Núcleo Supraóptico/citología , Núcleo Supraóptico/efectos de los fármacos , Vasopresinas/metabolismo
8.
Neuroscience ; 104(2): 539-50, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11377853

RESUMEN

Heat transduction mechanisms in primary nociceptive afferents have been suggested to involve a vanilloid receptor channel with high calcium permeability. To characterize the changes in free cytosolic calcium evoked by noxious heat stimuli (< or =51 degrees C, 10s), we performed microfluorometric measurements in acutely dissociated small dorsal root ganglion neurons (< or =32.5 microm) of adult rats using the dye FURA-2. Only neurons that responded with a reversible increase in intracellular calcium to high potassium were evaluated. Heat-induced calcium transients (exceeding mean + 3S.D. of the temperature dependence of the dye) were found in 66 of 105 neurons. These transients increased non-linearly with temperature. In contrast, heat-insensitive neurons showed a small linear increase of intracellular calcium throughout the range of 12-49 degrees C, similar to cardiac muscle cells. The vanilloid receptor agonist capsaicin induced calcium transients in 72 of 99 neurons. Capsaicin sensitivity and heat sensitivity were significantly associated (P<0.001, chi(2)-test), but 16 of 34 heat-insensitive cells responded to capsaicin and four of 49 heat-sensitive cells were capsaicin insensitive. The competitive vanilloid receptor antagonist capsazepine (10 microM) reversibly reduced the heat-induced calcium transients by 47+/-13%. In contrast, high potassium-induced calcium transients were not affected by pre-incubation with capsazepine. In calcium-free extracellular solution, the heat-induced rise in intracellular calcium was reduced by 76+/-5%. Heat-induced calcium transients were also reversibly reduced by 75+/-6% in sodium-free solution and by 62+/-7% with the L-type calcium channel blocker nifedipine (5 microM). These results indicate that noxious heat rapidly increases intracellular calcium in nociceptive primary sensory neurons. Heat-sensitive vanilloid receptors are involved in the induction of calcium transients, and calcium is also released from intracellular stores, but the main fraction of calcium passes through voltage-operated calcium channels.


Asunto(s)
Señalización del Calcio/fisiología , Citosol/metabolismo , Ganglios Espinales/metabolismo , Neuronas Aferentes/metabolismo , Nociceptores/metabolismo , Dolor/metabolismo , Receptores de Droga/metabolismo , Animales , Calcio/metabolismo , Canales de Calcio/efectos de los fármacos , Canales de Calcio/metabolismo , Señalización del Calcio/efectos de los fármacos , Capsaicina/farmacología , Células Cultivadas/citología , Células Cultivadas/efectos de los fármacos , Células Cultivadas/metabolismo , Citosol/efectos de los fármacos , Femenino , Colorantes Fluorescentes/farmacocinética , Fura-2/farmacocinética , Ganglios Espinales/citología , Ganglios Espinales/efectos de los fármacos , Calor/efectos adversos , Masculino , Miocardio/metabolismo , Neuronas Aferentes/citología , Neuronas Aferentes/efectos de los fármacos , Nociceptores/citología , Nociceptores/efectos de los fármacos , Dolor/fisiopatología , Potasio/farmacología , Ratas , Ratas Sprague-Dawley , Receptores de Droga/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Sensación Térmica/efectos de los fármacos , Sensación Térmica/fisiología
9.
J Physiol ; 528(Pt 3): 539-49, 2000 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-11060130

RESUMEN

Membrane currents evoked by repeated noxious heat stimuli (43-47 degrees C) of 3 s duration were investigated in acutely dissociated dorsal root ganglion (DRG) neurones of adult rats. The heat stimuli generated by a fast solution exchanger had a rise time of 114 +/- 6 ms and a fall time of 146 +/- 13 ms. When heat stimuli were applied to heat-sensitive small (< or = 32.5 microm) DRG neurones, an inward membrane current (I(heat)) with a mean peak of 2430 +/- 550 pA was observed (n = 19). This current started to activate and deactivate with no significant latency with respect to the heat stimulus. The peak of I(heat) was reached with a rise time of 625 +/- 115 ms. When the heat stimulus was switched off I(heat) deactivated with a fall time of 263 +/- 17 ms. During constant heat stimulation I(heat) decreased with time constants of 4-5 s (inactivation). At the end of a 3 s heat stimulus the peak current was reduced by 44 +/- 5 % (n = 19). Current-voltage curves revealed outward rectifying properties of I(heat) and a reversal potential of -6.3 +/- 2.2 mV (n = 6). Inactivation was observed at all membrane potentials investigated (-80 to 60 mV); however, inactivation was more pronounced for inward currents (37 +/- 5 %) than for outward currents (23 +/- 6 %, P < 0.05). When neurones were investigated with repeated heat stimuli (3 to 5 times) of the same temperature, the peak current relative to the first I(heat) declined by 48 +/- 6 % at the 3rd stimulus (n = 19) and by 54 +/- 18 % at the 5th stimulus (n = 4; tachyphylaxis). In the absence of extracellular Ca2+ (buffered with 10 mM EGTA) inactivation (by 53 +/- 6 %) and tachyphylaxis (by 42 +/- 7 % across three stimuli) were still observed (n = 8). The same was true when intracellular Ca2+ was buffered by 10 mM BAPTA (inactivation by 49 +/- 4 %, tachyphylaxis by 52 +/- 7 % across three stimuli; n = 13). Thus, inactivation and tachyphylaxis were mainly independent of intra- and extracellular Ca2+. These results indicate that inactivation and tachyphylaxis of heat-evoked inward currents can be observed in vitro, similar to adaptation and suppression of action potential discharges elicited by comparably fast heat stimuli in vivo. Whereas the voltage dependence of I(heat) resembles that of capsaicin-induced membrane currents (I(Caps)), the independence of inactivation and tachyphylaxis of I(heat) from calcium is in clear contrast to I(Caps). A similar difference in calcium dependence of inactivation has been reported between heat-evoked and capsaicin-induced currents through the cloned capsaicin receptor channel VR1. Thus, the properties of I(heat) and of VR1 largely account for the adaptation and suppression of heat-evoked nociceptor discharges.


Asunto(s)
Calor , Neuronas Aferentes/fisiología , Nociceptores/fisiología , Taquifilaxis/fisiología , Animales , Calcio/fisiología , Células Cultivadas , Conductividad Eléctrica , Espacio Extracelular/metabolismo , Femenino , Ganglios Espinales/citología , Ganglios Espinales/fisiología , Líquido Intracelular/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Factores de Tiempo
10.
J Physiol ; 526 Pt 1: 115-28, 2000 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-10878105

RESUMEN

Electrophysiological properties and ionic basis of subthreshold oscillation of the membrane potential were examined in 104 magnocellular neurones of the rat supraoptic nucleus using intracellular recording techniques in a brain slice preparation. Subthreshold oscillation of the membrane potential occurring in all neurones examined was voltage dependent. Oscillation was initiated 7-12 mV negative to the threshold of fast action potentials. Oscillation was the result of neither excitatory nor inhibitory synaptic activity nor of electric coupling. Frequency analyses revealed a broad band frequency distribution of subthreshold oscillation waves (range 10-70 Hz). The frequency band of 15-33 Hz was observed in neurones depolarized close to the threshold of discharge. Subthreshold oscillation was blocked by TTX (1.25-2.5 microM) as well as by TEA (15 mM). Subthreshold oscillation was not blocked by low Ca(2+)-high Mg(2+) superfusate, CdCl(2), TEA (1-4.5 mM), 4-aminopyridine, apamin, charybdotoxin, iberiotoxin, BaCl(2), carbachol and CsCl. During application of TTX, stronger depolarization induced high-threshold oscillation of the membrane potential at a threshold of about -32 mV. These oscillation waves occurred at a mean frequency of about 35 Hz and were blocked by CdCl(2). Effects of ion channel antagonists suggest that subthreshold oscillation is generated by the interaction of a subthreshold sodium current and a subthreshold potassium current. The generation of high-threshold oscillation during TTX involves a high-threshold calcium current. Subthreshold oscillation of the membrane potential may be important for the inter-neuronal synchronization of discharge and for the amplification of synaptic events.


Asunto(s)
Relojes Biológicos/fisiología , Neuronas/fisiología , Núcleo Supraóptico/fisiología , Anestésicos Locales/farmacología , Animales , Relojes Biológicos/efectos de los fármacos , Cadmio/farmacología , Calcio/metabolismo , Calcio/farmacología , Agonistas Colinérgicos/farmacología , Heptanol/farmacología , Técnicas In Vitro , Magnesio/metabolismo , Magnesio/farmacología , Masculino , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Neuronas/citología , Neuronas/efectos de los fármacos , Oscilometría , Bloqueadores de los Canales de Potasio , Procaína/farmacología , Ratas , Ratas Sprague-Dawley , Núcleo Supraóptico/citología , Núcleo Supraóptico/efectos de los fármacos , Tetraetilamonio/farmacología , Tetrodotoxina/farmacología
11.
J Neurophysiol ; 82(6): 2853-60, 1999 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-10601424

RESUMEN

Recent studies demonstrated that heat-sensitive nociceptive primary sensory neurons respond to the vanilloid receptor (VR) agonist capsaicin, and the first cloned VR is a heat-sensitive ion channel. Therefore we studied to what extent heat-evoked currents in nociceptive dorsal root ganglion (DRG) neurons can be attributed to the activation of native vanilloid receptors. Heat-evoked currents were investigated in 89 neurons acutely dissociated from adult rat DRGs as models for their own terminals using the whole cell patch-clamp technique. Locally applied heated extracellular solution (effective temperature approximately 53 degrees C) rapidly activated reversible and reproducible inward currents in 80% (62/80) of small neurons (< or = 32.5 microm), but in none of nine large neurons (P < 0.001, chi(2) test). Heat and capsaicin sensitivity were significantly coexpressed in this subpopulation of small DRG neurons (P < 0.001, chi(2) test). Heat-evoked currents were accompanied by an increase of membrane conductance (320 +/- 115%; mean +/- SE, n = 7), had a reversal potential of 5 +/- 2 mV (n = 5), which did not differ from that of capsaicin-induced currents in the same neurons (4 +/- 3 mV), and were carried at least by Na(+) and Ca(2+) (pCa(2+) > pNa(+)). These observations are consistent with the opening of temperature-operated nonselective cation channels. The duration of action potentials was significantly higher in heat-sensitive (10-90% decay time: 4.45 +/- 0.39 ms, n = 12) compared with heat-insensitive neurons (2.18 +/- 0.19 ms, n = 6; P < 0.005, Student's t-test), due to an inflection in the repolarizing phase. This property as well as capsaicin sensitivity and small cell size are characteristics of nociceptive DRG neurons. When coadministered with heat stimuli, the competitive VR antagonist capsazepine (1 microM to 1 mM) significantly reduced heat-evoked currents in a dose-dependent manner (IC(50) 13 microM, Hill slope -0.58, maximum effect 75%). Preincubation for 12-15 s shifted the IC(50) by approximately 0.5 log(10) units to an estimated IC(50) of approximately 4 microM. The noncompetitive VR antagonist ruthenium red (5 microM) significantly reduced heat-evoked currents by 33 +/- 6%. The effects of both VR antagonists were rapidly reversible. Our results provide evidence for a specific activation of native VRs in nociceptive primary sensory neurons by noxious heat. The major proportion of the rapid heat-evoked currents can be attributed to the activation of these temperature-operated channels, and noxious heat may be the signal detected by VRs under physiological conditions.


Asunto(s)
Calor , Neuronas Aferentes/efectos de los fármacos , Nociceptores/efectos de los fármacos , Receptores de Droga/antagonistas & inhibidores , Animales , Capsaicina/análogos & derivados , Capsaicina/farmacología , Relación Dosis-Respuesta a Droga , Electrofisiología , Femenino , Ganglios Espinales/citología , Ganglios Espinales/efectos de los fármacos , Masculino , Técnicas de Placa-Clamp , Ratas , Ratas Sprague-Dawley , Rojo de Rutenio/farmacología , Transducción de Señal/fisiología , Soluciones
12.
J Physiol ; 513 ( Pt 2): 493-506, 1998 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-9806998

RESUMEN

1. The pharmacological sensitivity of hyperpolarizing components of spike train after-potentials was examined in sixty-one magnocellular neurones of the rat supraoptic nucleus using intracellular recording techniques in a brain slice preparation. 2. In 26 % of all neurones a slow after-hyperpolarization (AHP) was observed in addition to a fast AHP. In 31 % of all neurones a depolarizing after-potential (DAP) was observed. 3. The fast AHP was blocked by apamin whereas the slow AHP was blocked by charybdotoxin (ChTX). The DAP was enhanced by ChTX or a DAP was unmasked if not present during the control period. 4. Low concentrations of TEA (0.15-1.5 mM) induced effects on the slow AHP and the DAP essentially resembling those of ChTX. The same was true for the effects of CoCl2 (1 mM). 5. Spike train after-potentials were not affected by either iberiotoxin (IbTX), a selective high-conductance potassium (BK) channel antagonist, or margatoxin (MgTX), a Kv1.3 alpha-subunit antagonist. 6. Kv1.3 alpha-subunit immunohistochemistry revealed that these units are not expressed in the somato-dendritic region of supraoptic neurones. 7. The effects of ChTX, IbTX, MgTX, TEA, CoCl2 and CdCl2 on spike train after-potentials are interpreted in terms of an induction of the slow AHP by the activation of calcium-dependent potassium channels of intermediate single channel conductance (IK channels). 8. The results suggest that at least the majority of supraoptic magnocellular neurones share the capability of generating both a slow AHP and a DAP. The slow AHP may act to control the expression of the DAP, thus regulating the excitability of magnocellular neurones. The interaction of the slow AHP and the DAP may be important for the control of phasic discharge.


Asunto(s)
Neuronas/fisiología , Canales de Potasio con Entrada de Voltaje , Núcleo Supraóptico/fisiología , Potenciales de Acción/fisiología , Animales , Apamina/farmacología , Caribdotoxina/farmacología , Electrofisiología , Inmunohistoquímica , Canal de Potasio Kv1.3 , Masculino , Neuronas/efectos de los fármacos , Canales de Potasio/metabolismo , Ratas , Ratas Sprague-Dawley , Núcleo Supraóptico/citología , Núcleo Supraóptico/efectos de los fármacos , Tetraetilamonio/farmacología
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