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Substance P Modulates Sensory Action Potentials in the Lamprey Via a Protein Kinase C‐Mediated Reduction of a 4‐Aminopyridine‐Sensitive Potassium Conductance
Author(s) -
Parker David,
Svensson Erik,
Grillner Sten
Publication year - 1997
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1997.tb01374.x
Subject(s) - chelerythrine , protein kinase c , protein kinase a , chemistry , substance p , protein kinase inhibitor , forskolin , medicine , endocrinology , biophysics , biochemistry , biology , receptor , kinase , neuropeptide
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 GDPβS. 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.