Inwardly Rectifying Current-Voltage Relationship of Small-Conductance Ca 2+-Activated K + Channels Rendered by Intracellular Divalent Cation Blockade

Abstract

Small conductance Ca 2+-activated K + channels (SK Ca channels) are a group of K +-selective ion channels activated by submicromolar concentrations of intracellular Ca 2+ independent of membrane voltages. We expressed a cloned SK Ca channel, rSK2, in Xenopus oocytes and investigated the effects of intracellular divalent cations on the current-voltage (I-V) relationship of the channels. Both Mg 2+ and Ca 2+ reduced the rSK2 channel currents in voltage-dependent manners from the intracellular side and thus rectified the I-V relationship at physiological concentration ranges. The apparent affinity of Mg 2+ was changed as a function of both transmembrane voltage and intracellular Ca 2+ concentration. Extracellular K + altered the voltage dependence as well as the apparent affinities of Mg 2+ binding from intracellular side. Thus, the inwardly rectifying I-V relationship of SK Ca channels is likely due to the voltage-dependent blockade of intracellular divalent cations and that the binding site is located within the ion-conducting pathway. Therefore, intracellular Ca 2+ modulates the permeation characteristics of SK Ca channels by altering the I-V relationship as well as activates the channel by interacting with the gating machinery, calmodulin, and SK Ca channels can be considered as Ca 2+-activated inward rectifier K + channels.