Protein kinase-mediated reciprocal modulatory changes in anesthetic sensitivity of (BK)-K+- and GABA-A receptor-gated conductances in guinea-pig sympathetic neurons
Wh. Stapelfeldt et Jm. Oleszewski, Protein kinase-mediated reciprocal modulatory changes in anesthetic sensitivity of (BK)-K+- and GABA-A receptor-gated conductances in guinea-pig sympathetic neurons, TOX LETT, 101, 1998, pp. 97-102
(1) The interaction of substance P (SP)-mediated synaptic transmission with
general anesthetics remains unknown. (2) Intracellular recordings were obt
ained from guinea-pig inferior mesenteric ganglion neurons to study monosyn
aptic responses to exogenous SP and GABA. (3) Propofol (1-100 mu M) caused
an increase in SP-evoked inward current responses and a concurrent decrease
in peak amplitude of the afterspike hyperpolarization of intermittently ev
oked action potentials. These effects were occluded by the (BK)-K+-channel-
selective blocker charybdotoxin (10 nM), and prevented by the protein kinas
e inhibitor staurosporine (100 nM). (4) Propofol also increased GABA-evoked
current (I-GABA) responses. (5) When elicited during a SP response, I-GABA
was significantly diminished compared to control. In the presence of staur
osporine (100 nM), the inhibitory effect of SP upon I-GABA was abolished, a
nd the propofol-induced augmentation of I-GABA was significantly increased.
(6) Thus, SP-evoked protein kinase activity produced reciprocal changes in
anesthetic sensitivity of (BK)-K+- and GABA A-receptor-gated currents of t
hese sympathetic neurons. (C) 1998 Elsevier Science Ireland Ltd. All rights
reserved.