Inhibition of protein kinase C differentially affects baroreflex inhibition and hypoxic excitation of medullary vasomotor neurons in rats.
We examined whether rapid sympathoexcitatory responses to hypoxia in rats resulting from excitation of reticulospinal vasomotor neurons of rostral ventrolateral medulla (RVL) results from activation of protein kinase C. In peripherally chemodenervated rats, the specific phosphokinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) administered intracisternally (i.c., 1 mumol), abolished responses of medullary vasomotor neurons and sympathetic nerves to baroreceptor activation, but did not attenuate excitation of RVL or sympathetic neurons to systemic hypoxia (100% N2 for 20 s). Responses of the vasomotor neurons to iontophoretically applied GABA were not attenuated by H-7. In slices, arachidonic acid (100 microM, 40 s) did not change membrane currents (VH = -70 mV) of RVL neurons in the presence tetrodotoxin (10 microM). The inward membrane currents (0.49 nA) induced by cyanide (300 microM, 40 s) were not reduced by H-7 (100 microM, 20 min). The results indicate that activation of protein kinase C does not underlie mechanisms involved in rapid hypoxic excitation of reticulospinal vasomotor neurons.
Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021.
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D003714:Denervation; D005154:Facial Nerve / Q000166:cytology / Q000502:physiology; D018756:GABA Antagonists; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007478:Iontophoresis; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018756:GABA Antagonists; D007546:Isoquinolines; D010879:Piperazines; D005680:gamma-Aminobutyric Acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C