Physiological implications of the Slack channel in the central and peripheral nervous systems

Abstract

The Slack channels, encoded by KCNT1, are found in neurons across the central nervous system (CNS) and peripheral nervous system (PNS), generating a delayed outward current known as sodium-activated potassium current (IK_Na). IK_Na plays a crucial role in shaping neuronal excitability and facilitating adaptation in response to sustained stimulation. Slack channels are crucial for neural plasticity and cognitive function; however, mutations in these channels cause profound learning and developmental abnormalities in humans. The physiological significance of Slack conductance in both systems is still unclear. This review provides a comprehensive overview of the role of Slack channels in both CNS and PNS, along with their associated modulators. It offers a summary of diseases that can result from abnormal expression of the Slack channel in both systems. Furthermore, identifying potent blockers and activators of Slack channels could greatly improve our understanding of Slack functions.