Presynaptic calcium channels mediating synaptic transmission in submucosal neurones of the guinea-pig caecum.
1. Intracellular recording techniques were used to examine the voltage-activated calcium channels mediating neurotransmitter release from nerve terminals of extrinsic, sympathetic origin and intrinsic (enteric) origin innervating submucosal neurones of the guinea-pig caecum. 2. The noradrenergic slow inhibitory postsynaptic potential (IPSP) was abolished by superfusion of omega-conotoxin (omega-CTX) GVIA (3-300 nM), with an apparent IC50 of 8.6 nM. Superfusion of omega-CTX MVIIC (500 nM) also suppressed the amplitude of slow IPSPs, but both omega-agatoxin IVA (100 nM) and nicardipine (1-10 microM) were ineffective. The hyperpolarization induced by exogenous noradrenaline was not affected by omega-CTX GVIA (100 nM). 3. In contrast to the slow IPSP, the amplitude of the cholinergic fast excitatory postsynaptic potential (EPSP) was partially inhibited, but not abolished, by omega-CTX GVIA (0.1-1 microM). Furthermore, omega-agatoxin IVA (0.1-1 microM) or omega-CTX MVIIC (0.1-1 microM) also affected the fast EPSP, but nicardipine (1-10 microM) was ineffective. In combination, omega-CTX GVIA (100 nM) and omega-agatoxin IVA (100 nM) inhibited the fast EPSP by 74 +/- 6 %; the residual fast EPSP was not affected by omega-CTX MVIIC (100 nM). The fast EPSP was completely abolished by low Ca2+, high Mg2+ Krebs solution or Krebs solution containing Co2+ (2 mM) and Cd2+ (400 microM). The depolarization induced by exogenous acetylcholine was not affected by either omega-CTX GVIA (100 nM), omega-agatoxin IVA (100 nM) or omega-CTX MVIIC (100 nM). 4. Taken together, these results suggest that, in the submucosal plexus of the guinea-pig caecum, release of noradrenaline from extrinsic nerve terminals is regulated by N-type calcium channels, whereas release of acetylcholine from intrinsic nerve terminals involves several types of calcium channel.
Cunningham
S M
SM
Department of Physiology, Kurume University School of Medicine, Asahi-machi, Kurume-shi, Japan. s.cunningham@abdn.ac.uk
Mihara
S
S
Higashi
H
H
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002432:Cecum / Q000294:innervation*; D006168:Guinea Pigs; D007413:Intestinal Mucosa / Q000294:innervation*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009529:Nicardipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D013111:Spider Venoms / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; D002104:Cadmium; C075851:omega-conotoxin-MVIIC; D020866:omega-Conotoxin GVIA; D009529:Nicardipine; D000109:Acetylcholine; D002118:Calcium; D009638:Norepinephrine