Effect of substance P on C1 and other bulbospinal cells of the RVLM in neonatal rats.
Sixty-two bulbospinal neurons were recorded in the rostral ventrolateral medulla (RVLM) of neonatal rats using patch electrodes. Sixty-one percent of the recorded neurons identified by histology contained tyrosine-hydroxylase (C1 cells). Substance P increased the spontaneous firing rate of all recorded cells but had no effect on spike configuration. The peptide depolarized neurons that were silenced by injection of hyperpolarizing current and increased their input resistance. All cells (n = 12) were activated by a neurokinin (NK)1 receptor agonist but most were unaffected by an NK2- or an NK2-selective compound. In voltage clamp, substance P produced a current that was linearly related to the membrane voltage. This current reversed polarity close to the potassium equilibrium potential in 11 of 23 cells. It reversed at more hyperpolarized potentials or not at all in the rest of the cells. In conclusion, substance P upregulates the intrinsic discharge rate of C1 and other putative sympathoexcitatory cells in neonatal rats. This effect is mediated via NK1 receptors. The depolarization is mediated by a reduction in resting potassium conductance and possibly by an additional cationic conductance. These results support the possibility that substance P could play a role "in vivo" in setting the basal level of discharge of the vasomotor cells of RVLM and therefore in regulating sympathetic vasomotor tone.
Li
Y W
YW
Department of Pharmacology, Health Sciences Center, University of Virginia, Charlottesville 22908, USA.
Guyenet
P G
PG
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology; D017097:Electric Impedance; D004594:Electrophysiology; D005260:Female; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018039:Receptors, Tachykinin / Q000819:agonists; D013373:Substance P / Q000494:pharmacology*
D018039:Receptors, Tachykinin; D013373:Substance P; D002118:Calcium