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

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 multilayer 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, Tukey–Kramer 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.