Protein kinase-mediated reciprocal modulatory changes in anesthetic sensitivity of (BK)-K+- and GABA-A receptor-gated conductances in guinea-pig sympathetic neurons.
(1) The interaction of substance P (SP)-mediated synaptic transmission with general anesthetics remains unknown. (2) Intracellular recordings were obtained from guinea-pig inferior mesenteric ganglion neurons to study monosynaptic responses to exogenous SP and GABA. (3) Propofol (1-100 microM) caused an increase in SP-evoked inward current responses and a concurrent decrease in peak amplitude of the afterspike hyperpolarization of intermittently evoked action potentials. These effects were occluded by the (BK)-K+-channel-selective blocker charybdotoxin (10 nM), and prevented by the protein kinase 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 staurosporine (100 nM), the inhibitory effect of SP upon I(GABA) was abolished, and 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 these sympathetic neurons.
Stapelfeldt
W H
WH
Department of Anesthesiology, Mayo Clinic Jacksonville, FL 32224, USA. stapelfeldt.wolf@mayo.edu
Oleszewski
J M
JM
D000200:Action Potentials / Q000187:drug effects; D000777:Anesthetics / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D015742:Propofol / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000502:physiology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D000777:Anesthetics; D018686:Anesthetics, Intravenous; D015221:Potassium Channels; D011963:Receptors, GABA-A; D013373:Substance P; D011494:Protein Kinases; D015742:Propofol