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Cardiovasc Res. 2001 Jul;51(1):59-70.

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

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Department of Cardiovascular Diseases and Etiology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.



Causal relation between changes in action potentials and activation of several ionic currents during hypoosmotic challenge was investigated.


We recorded changes in membrane potentials and currents during hypotonic stress in guinea-pig ventricular myocytes using whole-cell patch-clamp technique.


Exposure of ventricular myocytes to hypotonic solution (0.6 T) caused initial prolongation ( approximately 107% of control) of action potential duration at 90% repolarization (APD(90)) in 65% of examined myocytes. Later shortening (approximately 75% of control) of APD(90) and depolarization of resting potential (RP) (approximately 4 mV) developed in all cells. Initial prolongation of APD(90) in hypotonic solution was mainly caused by transient activation of Gd(3+)-sensitive non-selective cation (NSC) current. Late changes after approximately 180 s in hypotonic solution were sustained increase in slow component of delayed rectifier K(+) current (I(Ks)) in all cells, and activation of I(Clswell) in 40% of cells. Prevention of APD(90) shortening by chromanol, a selective blocker of I(Ks), was seen in about 40% of 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).


Initial prolongation followed by later shortening of APD in hypotonic solution are mostly caused by different sequences of NSC, I(Ks) and I(Clswell) currents activation. Depolarization of RP in hypotonic solution is probably due to dilution of subsarcolemmal K(+) concentration and/or change in permeability ratio for Na(+) and K(+).

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