Substance P modulates single-channel properties of neuronal nicotinic acetylcholine receptors.
Substance P (SP) is present in avian sympathetic ganglia and accelerates the decay rate of acetylcholine (ACh)-evoked macroscopic currents in sympathetic neurons. We demonstrate here that SP modulates ACh-elicited single channels in a manner consistent with an enhancement of ACh receptor (AChR) desensitization. Furthermore, since AChR channel function was monitored in cell-attached patches with SP applied to the extra-patch membrane, the peptide must act via a second messenger mechanism. SP specifically decreases the net ACh-activated single-channel current across the patch membrane by decreasing both channel opening frequency and mean open time kinetics. These experiments demonstrate that a peptide can modulate neuronal AChR function by a second messenger mechanism.
Simmons
L K
LK
Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Schuetze
S M
SM
Role
L W
LW
D000109:Acetylcholine / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D004553:Electric Conductivity; D004594:Electrophysiology / Q000379:methods; D005071:Evoked Potentials / Q000187:drug effects; D005728:Ganglia, Sympathetic / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D047428:Protein Kinase Inhibitors; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D015290:Second Messenger Systems; D019311:Staurosporine; D013373:Substance P / Q000494:pharmacology*
D000470:Alkaloids; D007473:Ion Channels; D047428:Protein Kinase Inhibitors; D011978:Receptors, Nicotinic; D013373:Substance P; D019311:Staurosporine; D000109:Acetylcholine