Abstract
Regulating membrane potential is key to cellular function. For many animal cells, resting membrane potential is predominantly driven by a family of K2P (two-pore domain) potassium channels. These channels are commonly referred to as leak channels, as their presence results in the membrane being permeable to K[+] ions. These channels, along with various pumps and exchangers, keep the cell resting membrane potential (Rp) relatively close to potassium's equilibrium potential (EK); however, in many cells, the resting membrane potential is more depolarized than the EK due to a small Na[+] ion leak. Raising [Ca[2+]]O (extracellular Ca[2+] concentration) can result in hyperpolarization of the membrane potential from the resting state. The mechanism for this hyperpolarization likely lies in the blockage of a Na[+] leak channel (NALCN) and/or voltage-gated Na[+] channels. The effects may also be connected to calcium-activated potassium channels. Using Drosophila melanogaster, we here illustrate that changing [Ca[2+]]O from 0.5 to 3 mM hyperpolarizes the muscle. Replacing NaCl with LiCl or choline chloride still led to hyperpolarization when increasing [Ca[2+]]O. Replacing CaCl2 with BaCl2 results in depolarization. K2P channel overexpression in the larval muscle greatly reduces the effects of [Ca[2+]]O on cell membrane potential, likely because potential is heavily driven by the EK in these muscles. These experiments provide an understanding of the mechanisms behind neuronal hypo-excitability during hypercalcemia, as well as the effects of altered expression of K2P channels on membrane potential.
