Differential involvement of N-type calcium channels in transmitter release from vasoconstrictor and vasodilator neurons.
1. The effects of calcium channel blockers on co-transmission from different populations of autonomic vasomotor neurons were studied on isolated segments of uterine artery and vena cava from guinea-pigs. 2. Sympathetic, noradrenergic contractions of the uterine artery (produced by 200 pulses at 1 or 10 Hz; 600 pulses at 20 Hz) were abolished by the N-type calcium channel blocker omega-conotoxin (CTX) GVIA at 1-10 nm. 3. Biphasic sympathetic contractions of the vena cava (600 pulses at 20 Hz) mediated by noradrenaline and neuropeptide Y were abolished by 10 nm CTX GVIA. 4. Neurogenic relaxations of the uterine artery (200 pulses at 10 Hz) mediated by neuronal nitric oxide and neuropeptides were reduced <50% by CTX GVIA 10-100 nm. 5. Capsaicin (3 microm) did not affect the CTX GVIA-sensitive or CTX GVIA-resistant neurogenic relaxations of the uterine artery. 6. The novel N-type blocker CTX CVID (100-300 nm), P/Q-type blockers agatoxin IVA (10-100 nm) or CTX CVIB (100 nm), the L-type blocker nifedipine (10 microm) or the 'R-type' blocker SNX-482 (100 nm), all failed to reduce CTX GVIA-resistant relaxations. The T-type channel blocker NiCl(2) (100-300 microm) reduced but did not abolish the remaining neurogenic dilations. 7. Release of different neurotransmitters from the same autonomic vasomotor axon depends on similar subtypes of calcium channels. N-type channels are responsible for transmitter release from vasoconstrictor neurons innervating a muscular artery and capacitance vein, but only partly mediate release of nitric oxide and neuropeptides from pelvic vasodilator neurons.
Department of Anatomy & Histology, Centre for Neuroscience, Flinders University, GPO Box 2100, Adelaide, SA 5001, Australia. Judy.Morris@flinders.edu.au
Judy L
JL
Morris
Daina I
DI
Ozols
Richard J
RJ
Lewis
Ian L
IL
Gibbins
Phillip
P
Jobling
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000294:innervation; D018377:Neurotransmitter Agents / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D014599:Uterus / Q000098:blood supply / Q000294:innervation; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014682:Vena Cava, Inferior / Q000294:innervation; D020960:omega-Conotoxins / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D018377:Neurotransmitter Agents; D020960:omega-Conotoxins