Actions of substance P on membrane potential and ionic currents in guinea pig stellate ganglion neurons.
Neuropeptides are known to modulate the excitability of mammalian sympathetic neurons by their actions on various types of K+ and Ca2+ channels. We used whole cell patch-clamp recording methods to study the actions of substance P (SP) on dissociated adult guinea pig stellate ganglion (SG) neurons. Under current-clamp conditions, SG neurons exhibited overshooting action potentials followed by afterhyperpolarizations (AHP). The K+ channel blocker tetraethylammonium (1 mM), the Ca2+ channel blocker Cd2+ (0.1-0.2 mM), and SP (500 nM) depolarized SG neurons, decreased the AHP amplitude, and increased the action potential duration. In the presence of Cd2+, the effect of SP on membrane potential and AHP was reduced. Under voltage-clamp conditions, several different K+ currents were observed, including a transient outward K+ conductance and a delayed rectifier outward K+ current (IK) consisting of Ca(2+)-sensitive [IK(Ca)] and Ca(2+)-insensitive components. SP (500 nM) inhibited IK. Pretreatment with Cd2+ (20-200 microM) or the high-voltage-activated Ca2+ channel blocker omega-conotoxin (10 microM) blocked SP's inhibitory effects on IK. This suggests that SP reduces IK primarily through the inhibition of IK(Ca) and that this may occur, in part, via a reduction of Ca2+ influx through voltage-dependent Ca2+ channels. SP's actions on IK were mediated by a pertussis toxin-insensitive G protein(s) coupled to NK1 tachykinin receptors. Furthermore, we have confirmed that 500 nM SP reduced an inward Cd(2+)- and omega-conotoxin-sensitive Ba2+ current in SG neurons. Thus the actions of SP on IK(Ca) may be due in part to a reduction in Ca2+ influx occurring via N-type Ca2+ channels. This study presents the first description of ionic currents in mammalian SG neurons and demonstrates that SP may modulate excitability in SG neurons via inhibitory actions on K+ and Ca2+ currents.
Gilbert
R
R
Department of Pharmacology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
Ryan
J S
JS
Horackova
M
M
Smith
F M
FM
Kelly
M E
ME
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D007477:Ions; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D011188:Potassium / Q000502:physiology; D018039:Receptors, Tachykinin / Q000502:physiology; D013233:Stellate Ganglion / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015220:Calcium Channels; D007477:Ions; D018039:Receptors, Tachykinin; D010566:Virulence Factors, Bordetella; D013373:Substance P; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D011188:Potassium