The Effects of Ca2+ on Membrane Potential with Altered Function of NALCN and K2P Channels

Abstract

Cells exhibit a membrane potential due to the differential distribution of ions and the density of channels, pumps, and exchangers. It is known in larval Drosophila that the membrane potential gravitates towards the equilibrium potential of K+ due to the high density of K2P channels. Higher extracellular Ca2+ ([Ca2+]o) tends to drive the resting membrane potential to a more negative state, while lowering it has an opposite effect. The expression of the K2P channel and NALCN was altered genetically to determine the sensitivity to changes in [Ca2+]o, and computational simulations using the theoretical Goldman-Hodgkin-Katz equation allowed estimating changes in ion (Na+) permeability due to altered function of the NALCN. Increasing [Ca2+]o hyperpolarized the membrane potential, and decreasing [Ca2+]o depolarized it, likely because Ca2+ ions block NALCN. An accessory protein to NALCN and NALCN itself were targeted by RNAi. Overexpression of K2P channels and decreased NALCN function reduced the effect of altered [Ca2+]o on membrane potential. Given the limited understanding of how altered membrane potentials affect cells, this study provides a foundation for future investigations into how cells respond to variations in [Ca2+]o under altered K2P and NALCN expression.