L-type Ca2+ channels and charybdotoxin-sensitive Ca2+-activated K+ channels are required for reduction of GABAergic activity induced by β2-adrenoceptor in the prefrontal cortex

Abstract

Whereas β2-adrenoceptor (β2-AR) has been reported to reduce GABAergic activity in the prefrontal cortex (PFC), the underlying cellular and molecular mechanisms have not been completely determined. Here, we showed that β2-AR agonist Clenbuterol (Clen) decreased GABAergic transmission onto PFC layer V/VI pyramidal neurons via a presynaptic mechanism without altering postsynaptic GABA receptors. Clen decreased the action potential firing rate but increased the burst afterhyperpolarization (AHP) amplitude in PFC interneurons. Application of L-type Ca²⁺ channel or charybdotoxin-sensitive Ca²⁺-activated K⁺ channel inhibitors blocked Clen-induced decreases in action potential firing rate, spontaneous inhibitory postsynaptic current (sIPSC) frequency and Clen-induced enhancement of AHP amplitude, suggesting that the effects of Clen involves L-type Ca²⁺ Channels and charybdotoxin-sensitive Ca²⁺-activated K⁺ channels. Our results provide a potential cellular mechanism by which Clen controls GABAergic neuronal activity in PFC.