Mechanism for Strict Regulation of Certain K+ Channels by Small, Fast Changes in Cell Volume

Abstract

A number of physiological processes, such as salt and water transport, neuronal activity, migration and apoptosis, involve changes in cell volume. The response of the cells to such challenges often is a regulatory volume decrease (RVD), a mechanism which involves activation of K+ channels. However, so far it has not been entirely clear which types of K+ channels should be considered sensitive to cell volume changes and, in particular, the mechanism for regulation has been obscure. To address this issue, we have co-expressed a number of K+ channels with aquaporins in Xenopus laevis oocytes and subsequently induced changes in cell voume by exposure to hypo- or hypertonic media. In all cases, the results are very clear; some K+ channels (e.g. KCNQ1 and 4, Kir4.1/5.1, Ca2+-activated IK and SK) are strictly regulated by small, fast changes in cell volume (approx. 5 %), whereas others are not (e.g. KCNQ2/3, Slo1 (BK) and Slo2.2 (slack)). Most recently, we have shown that the high-conductance slick channel (Slo 2.1) is dramatically stimulated (to 196 % of control) by cell swelling and inhibited (to 44 % of control) by a decrease in cell volume. Our results show that the mechanism responsible for the strict regulation of certain K+ channels by small, fast changes in cell volume, in some cases, involve the cytoskeleton.In contrast, cellular release of ATP is not involved, and the regulation is not mediated by membrane stretch. Our recent finding, that the high conductance slick channel is highly cell volume sensitive, will allow for further investigations at a single channel level.