Expression and Functional Phenotype of Mouse ERG K+ Channels in the Inner Ear: Potential Role in K+ Regulation in the Inner Ear

摘要

An outcome of the intricate K⁺ regulation in the cochlear duct is the endocochlear potential (EP), ∼80 mV, the “battery” that runs hair-cell transduction; however, the detailed molecular mechanisms for the generation of the EP remain unclear. We provide strong evidence indicating that the intermediate cells (ICs) of the stria vascularis (StV) express outward K⁺ current that rectifies inwardly at positive potentials. The channel belongs to the ether-a-go-go-related gene (erg) family of K⁺ channels. We cloned an ERG1a channel in the mouse inner ear (MERG1a). The cellular distribution of MERG1a in the cochlea displayed the highest levels of immunoreactivity in the ICs and modest reactivity in the marginal cells as well as in several extrastrial cells (e.g., hair cells). Functional expression of the StV-specific MERG1a channel reveals a current that activates at relatively negative potentials (approximately–50 mV) and shows rapid inactivation reflected as inward rectification at depolarized potentials. The current was sensitive to the methanesulfonanilide drug E-4031 (IC50, ∼165 nm) and the recombinant peptide rBeKm-1 (IC50, ∼16 nm), and the single-channel conductance in symmetrical K⁺ was ∼14 pS. The site of expression of MERG1a and its functional phenotype (e.g., modulation of the current by external K⁺) make it one of the most likely candidates for establishing the high throughput of K⁺ ions across ICs to generate EP. In addition, the property of the channel that produces marked K⁺ extrusion in increased external K⁺ may be important in shaping the dynamics of K⁺ cycling in the inner ear.