Neuronal type N calcium channels mediate norepinephrine release in isolated rabbit pulmonary artery.
Several types of voltage sensitive calcium channels (VSCC) including types N and Ln are present in varying degrees in neurons from different locations and they appear to differ from the Lm type VSCC on muscle cells. Omega conotoxin blocks N and Ln channels but not Lm channels. Verapamil blocks Ln and Lm but not N channels. The purpose of this study was to determine whether N or Ln channels mediate norepinephrine (NE) release in isolated rings of rabbit pulmonary artery. The release of endogenous NE from intramural sympathetic neurons was evoked by field electrical stimulation (ES) of the tissues. Conotoxin (10(-6) M) had no effect on contractions of rabbit pulmonary artery induced by 40 mM K+ or exogenous NE (10(-9)-10(-5) M) but significantly depressed the response to ES (21V, 0.5 msec pulse duration) at all stimulation frequencies (1-20Hz). Thus, the effects of conotoxin are restricted to the N and/or Ln calcium channels on neurons in this issue. Verapamil (5 x 10(-6) M) depressed 40 mM K(+)-induced contractions by 86 +/- 2% as well as contractions induced by endogenous (ES at 1-20 Hz) and exogenous NE (10(-9)-10(-5) M). Moreover, for contractions of equal magnitude, verapamil depressed the response to endogenous (ES) and exogenous NE to the same degree. Had Ln channels mediated NE release in the tissue, verapamil should have had a greater effect on ES-induced contractions because ES activates both pre- and post-junctional calcium channels whereas exogenous NE activates only post-junctional channels on smooth muscle cells. Thus, it appears that N-type calcium channels mediate NE release in rabbit pulmonary artery.
Russell
J A
JA
Department of Physiology, State University of New York, Buffalo.
Giese
E C
EC
Moore
T L
TL
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D009474:Neurons / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011651:Pulmonary Artery / Q000378:metabolism*; D011817:Rabbits; D014700:Verapamil / Q000494:pharmacology; D020960:omega-Conotoxins
D015220:Calcium Channels; D010456:Peptides, Cyclic; D020960:omega-Conotoxins; C053423:Conus magus toxin; D011433:Propranolol; D014700:Verapamil; D009638:Norepinephrine; D010646:Phentolamine