Voltage-dependent block of cardiac inward-rectifying potassium current by monovalent cations.
The inward-rectifying K+ current (IK1) in cat ventricular myocytes, like inward-rectifying K+ currents in many other preparations, exhibited a negative slope conductance region at hyperpolarized membrane potentials that was time-dependent. This was evident as an inactivation of inward current elicited by hyperpolarizing voltage-clamp pulses resulting in a negative slope region of the steady-state current-voltage relationship at potentials negative to -140 mV. Removing extracellular Na+ prevented the development of the negative slope in this voltage region, suggesting that Na+ can block IK1 channels in a time- and voltage-dependent manner. The time and voltage dependence of Cs+-induced block of IK1 was also examined. Cs+ blocked inward current in a manner similar to that of Na+, but the former was much more potent. The fraction of current blocked by Cs+ in the presence of Na+ was reduced in a time- and voltage-dependent manner, which suggested that these blocking ions compete for a common or at least similar site of action. In the absence of Na+, inactivation of IK1 could also be induced by both Cs+ and Li+. However, Li+ was less potent than Na+ in this respect. Calculation of the voltage sensitivity of current block by each of these ions suggests that the mechanism of block by each is similar.
Harvey
R D
RD
Department of Pharmacology, Northwestern University, Chicago, Illinois 60611.
Ten Eick
R E
RE
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002414:Cations, Monovalent; D002415:Cats; D002586:Cesium / Q000494:pharmacology; D004553:Electric Conductivity; D006352:Heart Ventricles / Q000378:metabolism; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology; D008564:Membrane Potentials; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology
D002414:Cations, Monovalent; D002586:Cesium; D008094:Lithium; D012964:Sodium; D011188:Potassium