Substance P modulates sensory action potentials in the lamprey via a protein kinase C-mediated reduction of a 4-aminopyridine-sensitive potassium conductance.
We have examined the effects of the tachykinin substance P on the action potential of lamprey mechanosensory dorsal cells. Substance P increased the spike duration and reduced the afterhyperpolarization. These effects were mimicked by stimulation of the dorsal root, which contains tachykinin-like immunoreactive fibres. The tachykinin antagonist spantide II blocked the effects of both substance P and dorsal root stimulation. The spike broadening was voltage-dependent, and was due to the reduction of a 4-aminopyridine-sensitive potassium conductance. The spike broadening was mimicked by G-protein activators and blocked by the G-protein inhibitor GDPbetaS. Pertussis toxin did not block the effects of substance P. The spike broadening was blocked by the protein kinase C and cAMP-dependent protein kinase inhibitor H7, and by the specific protein kinase C antagonist chelerythrine, but not by the cAMP and cGMP-dependent protein kinase inhibitor H8. The phorbol ester phorbol 12,13-dibutyrate mimicked and blocked the effects of substance P, supporting the role of protein kinase C in the spike modulation. The adenylate cyclase activator forskolin and the cAMP agonist SpcAMPs mimicked but did not block the effects of substance P on the spike duration, suggesting that protein kinase A also modulates the dorsal cell action potential, but that substance P acts independently of this pathway. Substance P also increased the excitability of the dorsal cells. This effect was blocked by 4-AP, PDBu and chelerythrine, but not by H8, suggesting that the increase in excitability shares the same intracellular and effector pathways as the spike broadening.
Parker
D
D
Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Svensson
E
E
Grillner
S
S
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D037361:Adenylate Cyclase Toxin; D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D019256:Cadmium Chloride / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007798:Lampreys; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009672:Notochord / Q000187:drug effects / Q000502:physiology*; D010455:Peptides; D037342:Pertussis Toxin; D010617:Phenanthridines / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology*; D019789:Tetraethylammonium / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014862:Wasp Venoms / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D010617:Phenanthridines; D015221:Potassium Channels; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D014862:Wasp Venoms; D006153:Guanosine Diphosphate; D013373:Substance P; D015240:Phorbol 12,13-Dibutyrate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019789:Tetraethylammonium; C023427:guanosine 5'-O-(2-thiodiphosphate); C037500:mastoparan; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C042867:spantide; D015761:4-Aminopyridine; C016299:chelerythrine; D037342:Pertussis Toxin; D011494:Protein Kinases; D011493:Protein Kinase C; D019256:Cadmium Chloride