5-HT₂ receptors-mediated modulation of voltage-gated K ⁺ channels and neurophysiopathological correlates

The activity of voltage-gated K⁺ channels (Kv) can be dynamically modulated by several events, including neurotransmitter stimulated biochemical cascades mediated by G protein-coupled receptors such as 5-HT ₂ receptors (5-HT₂Rs). Activation of 5-HT_2A/CR inhibits the Shaker-like K⁺ channels Kv1.1 and Kv1.2, and this modulation involves the dual coordination of both RPTPα and distinct tyrosine kinases coupled to this receptor; 5-HT₂Rs-mediated modulation of Kv channels controls glutamate release onto prefrontal cortex neurons that might play critical roles in neurophysiological, neurological, and psychiatric conditions. Noticeably, hallucinogens modulate Kv channel activity, acting at 5-HT₂R. Hence, comprehensive knowledge of 5-HT₂R signaling through modulation of distinct K⁺ channels is a pivotal step in the direction that will enable scientists to discover novel 5-HT functions and dysfunctions in the brain and to identify original therapeutic targets.