Substance P modulates nicotinic responses of intracardiac neurons to acetylcholine in the guinea pig.
Application of substance P (SP) to intracardiac neurons of the guinea pig causes slow depolarization and increases neuronal excitability. The present study was done to determine the influence of SP on fast excitatory responses of intracardiac neurons to ACh. Intracellular recording methods were used to measure responses of intracardiac neurons in whole mount preparations of atrial ganglionated nerve plexus from guinea pig hearts. Local pressure ejection of 100 microM SP (1 s) from a glass micropipette caused slow depolarization of all neurons (n = 38) and triggered action potential generation in 47% of the cells tested. Bath application of SP (0.5-100 microM) caused a dose-dependent depolarization of intracardiac neurons but rarely evoked action potentials, even at the highest concentration. However, such treatment with SP enhanced nicotinic responses evoked by local pressure ejections of ACh (10 mM, 10- to 100-ms duration) in 77% of intracardiac neurons studied (n = 52). A significant increase in amplitude of ACh-evoked fast depolarization occurred during treatment with 0.5 microM SP (13.0 +/- 1.8 mV for control vs. 17.7 +/- 1.9 mV with SP present, n = 7, P = 0.019). At higher concentrations of SP, enhancement of the response to ACh resulted mainly in action potential generation. However, responses to ACh were attenuated by SP in 15% of the intracardiac neurons studied. This attenuation occurred primarily during exposure to 10 and 100 microM SP and was manifest as a reduction in amplitude of nicotinic fast depolarization or inhibition of ACh-evoked action potentials. These findings support the conclusion that SP could function as a neuromodulator and neurotransmitter in intracardiac ganglia of the guinea pig.
Zhang
L
L
Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Tompkins
J D
JD
Hancock
J C
JC
Hoover
D B
DB
D000109:Acetylcholine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D006168:Guinea Pigs; D006321:Heart / Q000294:innervation*; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology*
D011978:Receptors, Nicotinic; D013373:Substance P; D000109:Acetylcholine