Tachykinin-induced activation of non-specific cation conductance via NK3 neurokinin receptors in guinea-pig intracardiac neurones.
1. Whole mount preparations from guinea-pig hearts were used to characterize the receptors and ionic mechanisms mediating the substance P (SP)-induced depolarization of parasympathetic postganglionic neurones of the cardiac ganglion. 2. Measurement of the amplitude of depolarization in response to superfusion of different tachykinin agonists (neurokinins A (NKA) and B (NKB), SP, and senktide) gave a rank-order potency of NKB = senktide > NKA > SP, indicating involvement of an NK3 receptor. The use of the selective tachykinin receptor antagonists SR 140333, SR 48986, and SR 142801 demonstrated that only the NK3 receptor antagonist SR 142801 inhibited the SP-induced depolarization. 3. The SP-induced depolarization was not inhibited by Ba2+, TEA, or niflumic acid, or altered by reduced Cl- solutions, but was attenuated in reduced Na+ solutions. Single electrode voltage clamp studies demonstrated that the SP-induced inward current increased in amplitude at more negative potentials, had a reversal potential of approximately 0 mV, and was reduced in amplitude in reduced Na+ solutions. 4. We conclude that the SP-induced depolarization in guinea-pig postganglionic parasympathetic neurones of the cardiac ganglion is due to NK3-mediated activation of a non-selective cation conductance.
Hardwick
J C
JC
Department of Anatomy and Neurobiology, University of Vermont, Burlington 05405, USA.
Mawe
G M
GM
Parsons
R L
RL
D000818:Animals; D001464:Barium / Q000378:metabolism; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000294:innervation*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D018042:Receptors, Neurokinin-3 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D007473:Ion Channels; D010880:Piperidines; D018042:Receptors, Neurokinin-3; D015320:Tachykinins; D013757:Tetraethylammonium Compounds; D001464:Barium; D013373:Substance P; C091554:SR 142801