Cell-volume regulation by swelling-activated chloride current in guinea-pig ventricular myocytes

The cell-volume regulation by swelling-activated Cl- current (I(Cl,swell)) was studied in guinea pig ventricular myocytes, using a microscopic video-image analysis. We have previously shown that in ventricular cells depolarized in high-K+ ([K+]o>45 mM) solution, an activation of the cyclic AMP-dependent Cl- current (I(Cl,cAMP)) leads to cell swelling. We first investigated the mechanism underlying the I(Cl,cAMP)-independent recovery (shrinkage) of the swollen cells. They shrank when the membrane potential (Vm) was made negative to the equilibrium potential of Cl- (ECl) by lowering [K+]o or [Cl-]o in the high-K+ solution. This shrinkage was attenuated by the inhibitors (DIDS, glibenclamide, furosemide) of swelling-activated Cl- current (I(Cl,swell)). These findings suggested an involvement of I(Cl,swell) in the observed isosmotic cell shrinkage. On the other hand, an application of hyposmotic (70% of control) solution to the cells at normal [K+]o (ECl>Vm) induced a cell swelling, and the swollen cells underwent a slight but definite spontaneous cell shrinkage during hyposmotic challenge, indicating the operation of the mechanism of regulatory volume decrease (RVD). This RVD was pronounced at low [Cl-]o, at which ECl was much more positive than Vm. On the contrary, when the hyposmotic solution was applied to the cells at high [K+]o, at which ECl was negative to Vm, the cells swelled vigorously and monotonically without showing RVD, the swelling being much greater than that seen at normal [K+]o. Both the RVD at normal [K+]o and the extra cell swelling at high [K+]o were suppressed by DIDS. These results suggest that I(Cl,swell) activated by cell swelling can shrink or inflate the cardiac cells under hyposmotic as well as isosmotic conditions, depending on Vm and ECl.