Ionic basis for membrane potential changes induced by hypoosmotic stress in guinea-pig ventricular myocytes

Objective: Causal relation between changes in action potentials and activat ion of several ionic currents during hypoosmotic challenge was investigated . Methods: We recorded changes in membrane potentials and currents during h ypotonic stress in guinea-pig ventricular myocytes using whole-cell patch-c lamp technique. Results: Exposure of ventricular myocytes to hypotonic solu tion (0.6 T) caused initial prolongation (similar to 107% of control) of ac tion potential duration at 90% repolarization (APD(90)) in 65% of examined myocytes. Later shortening (similar to 75% of control) of APD(90) and depol arization of resting potential (RP) (similar to 4 mV) developed in all cell s. Initial prolongation of APD(90) in hypotonic solution was mainly caused by transient activation of Gd3+-sensitive non-selective cation (NSC) curren t. Late changes after similar to 180 s in hypotonic solution were sustained increase in slow component of delayed rectifier K+ current (I-Ks) in all c ells, and activation of I-Clswell in 40% of cells. Prevention of APD(90) sh ortening by chromanol. a selective blocker of I-Ks, was seen in about 40% o f myocytes due to short APD in our experimental conditions. Application of 1 mM anthracene-9-carboxylic acid (9-AC) partially inhibited APD shortening in three of seven cells. Depolarization of RP was unaffected by the above- mentioned drugs, but was dependent on [K+](o). Conclusions: Initial prolong ation followed by later shortening of APD in hypotonic solution are mostly caused by different sequences of NSC, I-Ks and I-Clswell currents activatio n. Depolarization of RP in hypotonic solution is probably due to dilution o f subsarcolemmal K+ concentration and/or change in permeability ratio for N a+ and K+. (C) 2001 Elsevier Science B.V. All rights reserved.