IK channels are involved in the regulatory volume decrease in human epithelial cells

Parallel activation of Ca(2+)-dependent K(+) channels and volume-sensitive Cl(-) channels is known to be responsible for KCl efflux during regulatory volume decrease (RVD) in human epithelial Intestine 407 cells. The present study was performed to identify the K(+) channel type. RT-PCR demonstrated mRNA expression of Ca(2+)-activated, intermediate conductance K(+) (IK), but not small conductance K(+) (SK1) or large conductance K(+) (BK) channels in this cell line. Whole cell recordings showed that ionomycin or hypotonic stress activated inwardly rectifying K(+) currents that were reversibly blocked by IK channel blockers [clotrimazole (CLT) and charybdotoxin] but not by SK and BK channel blockers (apamin and iberiotoxin). Inside-out recordings revealed the existence of CLT-sensitive single K(+)-channel activity, which exhibited an intermediate unitary conductance (30 pS at -100 mV). The channel was activated by cytosolic Ca(2+) in inside-out patches and by a hypotonic challenge in cell-attached patches. The RVD was suppressed by CLT, but not by apamin or iberiotoxin. Thus we conclude that the IK channel is involved in the RVD process in these human epithelial cells.