Fig. 2.

a In the challenged auditory system leading to age-related hearing loss (ARHL), the key causing factors are postulated to be lifetime noise exposure, hereditary predisposition, and the accumulation of reactive oxygen species (ROS). b In a healthy outer hair cell (OHC), potassium ions (K⁺) enter the cell through apical mechanosensitive channels and are then transported to the supporting cells through K_V7.4 (KCNQ4, green) channels on the basolateral membrane of OHC. However, in the challenged system, the expression of K_V7.4 is reduced, resulting in a poor K⁺ efflux. This state can be influenced by the addition of K⁺ channel modulators (green circle) in a way where cell surface expression remains stable but the efflux rate can be increased. c In fast-spiking, parvalbumin-positive interneurons, K_V3.1 (KCNC1, red) is required for the high-frequency repetitive firing. A decline in K_V3.1 cell surface expression leads to an incapacity of neurons to maintain high-frequency firing action potentials. Modulators that bind to K_V3.1 (red circle) may lower action potential latencies and duration and increase the firing pattern of these neurons