Modulation by cAMP of a slowly activating potassium channel expressed in Xenopus oocytes

Abstract

When expressed in the Xenopus oocyte, the minK protein induces a slowly activating voltage-dependent potassium current (Isk). We studied the modulation of this current by altering intracellular cAMP levels and found that the amplitude of Isk is dramatically increased by treatments that raise cAMP levels and decreased by agents that lower cAMP levels. Preinjection of a protein inhibitor of the cAMP-dependent protein kinase blocked the effects of increased cAMP levels. There were no changes in the voltage dependence or kinetics of Isk. Mutations that eliminate a potential phosphorylation site on the minK protein did not block the effects of activating the kinase. In addition, the membrane capacitance of the oocyte increased and decreased in parallel with Isk. Our results fit a mechanism in which channel proteins are selectively inserted into and removed from the plasma membrane in response to changes in kinase activity.

KvLQT1, a voltage-gated potassium channel responsible for human cardiac arrhythmias

“…Thus, although the relationship to the disease remains to be clarified, we have shown that a channel involved in LQTS indeed is regulated by sympathetic stimulation. Interestingly, slowly activating delayed rectifier currents (I Ks ) recorded from oocytes injected with cRNA encoding minK also are stimulated by cAMP (17).…”

Molecular Basis of Voltage-Dependent Potassium Currents in Porcine Granulosa Cells

“…Our identification not only of KCNQ1 and KCNE1 as the molecular correlates of GC I Ks but also of 293B, L-735,821, and L-768,673 as specific antagonists of the current, will facilitate further investigation of its functional role. Additional experiments will be required to determine the basis for tissue-specific differences in I Ks modulation, particularly to address the discrepant effects of cAMP on GC I KS compared with recombinant KCNQ1/KCNE1 currents (Blumenthal and Kaczmarek, 1992) and native cardiac currents in guinea pig (Walsh et al, 1989) and pig (L. C. Freeman, unpublished observations).…”

Effects of [Ca2+]i and temperature on minK channels expressed in Xenopus oocytes

“…MinK channels expressed in Xenopus oocytes show a similar slow activation as IK~ in guinea pig cardiac myocytes. In addition, the RNA encoding mink channels has been found in heart tissue of several species including guinea pig ( [4,6] minK channels and/Ks by second messengers has also been described [6,7,8,18]. Most recently, an identical sensitivity to novel class III antiarrhythmic compounds has been observed for Ir~s in guinea pig cardiac myocytes and minK channels expressed in Xenopus oocytes [19].…”