Contribution of a swelling-activated chloride current to changes in the cardiac action potential

The purpose of this investigation was to determine to what extent the swelling-activated Cl^- current (I(Cl,swell)) contributes to swelling- induced changes in the resting membrane potential and action potential duration (APD) in ventricular myocytes. Action potentials were recorded from guinea pig ventricular myocytes using conventional whole cell recording techniques. Cell swelling caused initial lengthening followed by a variable shortening of APD. In 59% of cells this secondary APD shortening had a 4,4'- diisothiocyanostilbene-2.2'-disulfonic acid (DIDS)-sensitive component, consistent with a contribution from I(Cl,swell). Furthermore, DIDS partially antagonized the depolarization of the resting membrane potential that occurred during cell swelling. We have modeled the I(Cl,swell) using the Oxsoft Heart computer program. Action potential changes predicted by the model agree well with the observed DIDS-sensitive component of the change in the action potential during cell swelling. We conclude that activation of I(Cl,swell) contributes to shortening of APD and depolarization of the resting membrane potential during cell swelling in cardiac myocytes.