On the mechanism of cesium-induced voltage and current tails in single ventricular myocytes.
The mechanisms by which different concentrations of cesium modify membrane potentials and currents were investigated in guinea pig single ventricular myocytes. In a dose-dependent manner, cesium reversibly decreases the resting potential and action potential amplitude and duration, and induces a diastolic decaying voltage tail (Vex), which increases at more negative and reverses at less negative potentials. In voltage-clamped myocytes, Cs+ increases the holding current, increases the outward current at plateau levels while decreasing it at potentials closer to resting potential, induces an inward tail current (Iex) on return to resting potential and causes a negative shift of the threshold for the inward current. During depolarizing ramps, Cs+ decreases the outward current negative to inward rectification range, whereas it increases the current past that range. During repolarizing ramps, Cs+ shifts the threshold for removal of inward rectification negative slope to less negative values. Cs+-induced voltage and current tails are increased by repetitive activity, caffeine (5 mM) and high [Ca2+]O (8.1 mM), and are reduced by low Ca2+ (0.45 mM), Cd2+ (0.2 mM) and Ni2+ (2 mM). Ni2+ also abolishes the tail current that follows steps more positive than ECa. We conclude that Cs+ (1) decreases the resting potential by decreasing the outward current at more negative potentials, (2) shortens the action potential by increasing the outward current at potentials positive to the negative slope of inward rectification, and (3) induces diastolic tails through a Ca2+-dependent mechanism, which apparently is an enhanced electrogenic Na-Ca exchange.
Shen
J B
JB
Department of Physiology and Pharmacology, State University of New York, Health Science Center, Brooklyn, NY 11203, USA.
Vassalle
M
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002586:Cesium / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D002586:Cesium; D009532:Nickel; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium