Active K+ secretion through multiple KCa-type channels and regulation by IKCa channels in rat proximal colon.

Colonic K+ secretion stimulated by cholinergic agents requires activation of muscarinic receptors and the release of intracellular Ca2+. However, the precise mechanisms by which this rise in Ca2+ leads to K+ efflux across the apical membrane are poorly understood. In the present study, Northern blot analysis of rat proximal colon revealed the presence of transcripts encoding rSK2 [small conductance (SK)], rSK4 [intermediate conductance (IK)], and rSlo [large conductance (BK)] Ca2+-activated K+ channels. In dietary K+-depleted animals, only rSK4 mRNA was reduced in the colon. On the basis of this observation, a cDNA encoding the K+ channel rSK4 was cloned from a rat colonic cDNA library. Transfection of this cDNA into Chinese hamster ovary (CHO) cells led to the expression of Ca2+-activated K+ channels that were blocked by the IK channel inhibitor clotrimazole (CLT). Confocal immunofluorescence confirmed the presence of IK channels in proximal colonic crypts, and Western blotting demonstrated that IK protein sorted to both the apical and basolateral surfaces of colonic epithelia. In addition, transcellular active K+ secretion was studied on epithelial strips of rat proximal colon using unidirectional 86Rb+ fluxes. The addition of thapsigargin or carbachol to the serosal surface enhanced net 86Rb+ secretion. The mucosal addition of CLT completely inhibited carbachol-induced net 86Rb+ secretion. In contrast, only partial inhibition was observed with the BK and SK channel inhibitors, iberiotoxin and apamin, respectively. Finally, in parallel with the reduction in SK4 message observed in animals deprived of dietary K+, carbachol-induced 86Rb+ secretion was abolished in dietary K+-depleted animals. These results suggest that the rSK4 channel mediates K+ secretion induced by muscarinic agonists in the rat proximal colon and that transcription of the rSK4 channel is downregulated to prevent K+ loss during dietary K+ depletion.

In rat inner medullary collecting duct, NH uptake by the Na,K-ATPase is increased during hypokalemia.

In rat terminal inner medullary collecting duct (tIMCD), the Na,K-ATPase mediates NH uptake, which increases secretion of net H(+) equivalents. K(+) and NH compete for a common binding site on the Na,K-ATPase. Therefore, NH uptake should increase during hypokalemia because interstitial K(+) concentration is reduced. We asked whether upregulation of the Na,K-ATPase during hypokalemia also increases basolateral NH uptake. To induce hypokalemia, rats ate a diet with a low K(+) content. In tIMCD tubules from rats given 3 days of dietary K(+) restriction, Na,K-ATPase beta(1)-subunit (NK-beta(1)) protein expression increased although NK-alpha(1) protein expression and Na,K-ATPase activity were unchanged relative to K(+)-replete controls. However, after 7 days of K(+) restriction, both NK-alpha(1) and NK-beta(1) subunit protein expression and Na,K-ATPase activity increased. The magnitude of Na,K-ATPase-mediated NH uptake across the basolateral membrane (J) was determined in tIMCD tubules perfused in vitro from rats after 3 days of a normal or a K(+)-restricted diet. J was the same in tubules from rats on either diet when measured at the same extracellular K(+) concentration. However, in either treatment group, increasing K(+) concentration from 10 to 30 mM reduced J >60%. In conclusion, with 3 days of K(+) restriction, NH uptake by Na,K-ATPase is increased in the tIMCD primarily from the reduced interstitial K(+) concentration.

The absorption of iron, calcium, phosphorus, magnesium, copper and zinc in the jejunum-ileum of control and iron-deficient rats.

The effects of iron deficiency on the absorption of different dietary sources of iron were studied, together with the interactions between iron, calcium, phosphorus, magnesium, copper and zinc in the jejunum-ileum of control and iron-deficient rats. In this study, three perfusion solutions containing different iron sources: ferric citrate, haemoglobin, and equal parts of ferric citrate and haemoglobin were used. In addition, the same perfusion solutions were used with and without 2,4-dinitrophenol, an inhibitor of oxidative phosphorylation. Iron absorption in anaemic rats was greater than in the controls, except after perfusion with solutions containing haemoglobin. The absorption of calcium, copper and zinc in iron-deficient animals was not significantly affected, while the absorption of phosphorus and magnesium increased, with respect to animals in the control group. After perfusion with solutions containing haemoglobin, the absorption values of calcium, copper and zinc were lower than after ferric citrate in both groups (control and iron-deficient rats).

Tratamiento de la hipertensión arterial esencial con dieta rica en potasio

Con el objetico de determinar el efecto sobre la presión arterial de una dieta rica en potasio en pacientes adultos con hipertensión arterial leve, sin modificaciones en el consumo habitual de sodio y que no se encuentren bajo tratamiento farmacológico, se estudiaron 24 pacientes, distribuidos aleatoriamente en dos grupos. Al grupo de estudio se le ordenó iuna dieta rica en potasio (alrededor de 2mEq/kg-día), durante ocho semanas. A todos los pacientes se les recomendó continuar las medidas no farmacológicas usuales. Se midió la presión arterial semanalmente en el domicilio del paciente, así como el potasio y el sodio en suero y orina al inicio y en las semanas dos,cuatro y ocho. En todos los sujetos se observó disminución en las cifras tensionales; sin embargo, la reducción de la presión arterial sistólica en el grupo de estudio fue de 7.9ñ7.99 vs 18ñ8.72 mm Hg en el control (p<0.023); mientras que la reducción en la presión diastólica fue de 8.28ñ5.89 Vs 2.86ñ4.31 mm Hg,respectivamente (p<10elevada a la - 7). El efecto sobre la presión arterial tiende a estabilizarse a partir de la cuarta semana de tratamiento. No hubo modificaciones en los niveles séricos de potasio. Se observó incremento en la excreción de potasio en el grupo de estudio de 10.09ñ25.5 vs -4.98ñ19.15 mEq/L en el control (p<0,069). Se concluye que una dieta rica en potasio contribuye favorablemente para el control de la hipertensión arterial esencial y es una medida segura en pacientes con función renal normal