Figure 1.

Potassium channel activation during action potential (AP) firing in sensory neurons. A depiction of the sequential engagement of different K⁺ channels during neuronal activity, and typical effects of K⁺ channel opening on AP waveform and frequency (inset). The resting membrane potential (RMP) is primarily stabilized by two-pore K⁺ (K_2P) channels and K_v7 background conductance, whereas K_ATP channels may also contribute in large neurons [95]. Basal excitability is also influenced by the opening of low-threshold K_v1 and K_v4 channels which filter out small depolarizations and therefore control the number of triggered APs. K_v4 channels are normally inactivated at RMP and require prior hyperpolarization (achieved during AP generation) to remove this steady-state inactivation. Once activated, however, K_v4 and other A-type channels may modulate firing threshold as well as repetitive spiking rate owing to their very fast kinetics [inset (A)] [47]. Following suprathreshold stimulation and initiation of an AP, high-threshold K_v3 channels open to limit AP duration and ensure quick recovery of voltage-gated Na⁺ channels from inactivation [inset (B)]. K_v2 channels are also high-threshold but with much slower activation and inactivation kinetics; they mainly contribute to the repolarizing/after-hyperpolarizing phases and are hence important for regulating interspike interval and conduction fidelity during sustained stimulation [inset (B)] [38]. Upon neuronal activity, Ca²⁺-activated K⁺ channels are engaged during repolarization (BK_CA) and after-hyperpolarization (SK_CA) to provide feedback inhibition at nerve terminals by restricting AP duration and thus neurotransmitter release [(inset (B)]. It is emphasized that this schematic is a simplified representation of most prominent K⁺ channel contributions to AP firing, based on in vitro assessment of recombinant counterparts. In vivo, however, the oligomeric composition, association with auxiliary proteins, post-translational modifications, and regulation by intracellular messengers can yield divergent biophysical properties. K⁺ channel opening will also have concurrent effects on the function of other ion channels, for instance by affecting their inactivation. For this reason the combined effect on firing behavior in a physiological context is often hard to predict. Abbreviations: BK_CA, big conductance and SK_CA, small conductance Ca²⁺-activated K⁺ channels.