Work

Modulation of BK-like potassium currents by ketamine in rat cochlear outer hair cells

Year: 2026

Type: article

Abstract: Ketamine is widely used as an anesthetic agent, yet its cellular effects on the auditory system, particularly on cochlear outer hair cells (OHCs), remain incompletely understood. In this study, we investigated the electrophysiological effects of ketamine on isolated OHCs from young Sprague Dawley rats using whole-cell patch-clamp techniques. OHCs were acutely dissociated and exposed to ketamine at varying concentrations to evaluate its impact on membrane currents. Ketamine produced a dose- and voltage-dependent reduction in outward membrane currents, particularly at membrane potentials more positive than –36 mV. Pharmacological blockade with iberiotoxin and ion substitution experiments using intracellular Cs + support that the ketamine-sensitive current is predominantly mediated by BK-like Ca 2+ -activated K + channels. Ketamine had minimal effects on resting membrane potential and on voltage-activated K + currents at hyperpolarized potentials, indicating selective modulation of depolarization-activated conductances. Acetylcholine (ACh)-evoked outward currents recorded at a depolarized holding potential (+ 3 mV) were not significantly altered by ketamine. Under these conditions, the measured current primarily reflects secondary Ca 2+ -activated K + channel activity rather than direct α9α10 nicotinic receptor-mediated currents. Therefore, the present experimental design does not allow determination of whether ketamine directly affects α9α10 receptor function. These findings demonstrate that ketamine modulates BK-like potassium currents in OHCs and may influence cochlear electrophysiological function. However, the precise mechanism—whether through direct channel interaction or indirect modulation via calcium signaling—remains to be determined.

Source: Molecular Brain

DOI: 10.1186/s13041-026-01306-1