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 (E(K)); however, in many cells, the resting membrane potential is more depolarized than the E(K) 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 CaCl(2) with BaCl(2) 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 E(K) 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.