The unique ion permeability profile of cochlear fibrocytes and its contribution to establishing their positive resting membrane potential

摘要

Eukaryotic cells exhibit negative resting membrane potential (RMP) owing to the high K+ permeability of the plasma membrane and the asymmetric [K+] between the extracellular and intracellular compartments. However, cochlear fibrocytes, which comprise the basolateral surface of a multi-layer epithelial-like tissue, exhibit a RMP of +5 to +12 mV in vivo. This positive RMP is critical for the formation of an endocochlear potential (EP) of +80 mV in a K+-rich extracellular fluid, endolymph. The epithelial-like tissue bathes fibrocytes in a regular extracellular fluid, perilymph, and apically faces the endolymph. The EP, which is essential for hearing, represents the potential difference across the tissue. Using in vivo electrophysiological approaches, we describe a potential mechanism underlying the unusual RMP of guinea pig fibrocytes. The RMP was + 9.0 +/- 3.7 mV when fibrocytes were exposed to an artificial control perilymph (n = 28 cochleae). Perilymphatic perfusion of a solution containing low [Na+] (1 mM) markedly hyperpolarized the RMP to -31.1 +/- 11.2 mV (n = 10; p < 0.0001 versus the control, TukeyKramer test after one-way ANOVA). Accordingly, the EP decreased. Little change in RMP was observed when the cells were treated with a high [K+] of 30 mM (+ 10.4 +/- 2.3 mV; n= 7; p = 0.942 versus the control). During the infusion of a low [Cl-] solution (2.4 mM), the RMP moderately hyperpolarized to -0.9 +/- 3.4 mV (n = 5; p < 0.01 versus the control), although the membranes, if governed by Cl-permeability, should be depolarized. These observations imply that the fibrocyte membranes are more permeable to Na+ than K+ and Cl-, and this unique profile and [Na+] gradient across the membranes contribute to the positive RMP.