MUSCARINE INCREASES A VOLTAGE-INDEPENDENT POTASSIUM CONDUCTANCE THROUGH AN M(4) RECEPTOR IN RAT DORSOLATERAL SEPTAL NUCLEUS NEURONS

The direct effect of muscarine on neurons of the rat dorsolateral sept al nucleus (DLSN) was examined by using conventional microelectrode an d voltage-clamp techniques. Muscarine (1-50 mu M) caused a hyperpolari zation accompanied by an increase of a voltage-independent potassium c onductance. Pirenzepine competitively antagonized the muscarine-induce d hyperpolarization with an apparent dissociation constant (K-d) Value of 54 nM. Furthermore, intracellular loading with GTP gamma S, a non- hydrolyzable GTP analog, blocked irreversibly the muscarine-induced hy perpolarization. In addition, pretreatment of neurons with pertussis t oxin (PTX) prevented the hyperpolarization produced by muscarine. Thes e results suggest that muscarine hyperpolarizes DLSN neurons via a vol tage-independent potassium conductance by acting at M(4) subtype recep tors which are coupled to a PTX-sensitive G-protein in DLSN neurons.