SELECTIVITY OF ω-CONOTOXIN GVIA FOR N-TYPE CALCIUM CHANNELS IN RAT ISOLATED SMALL MESENTERIC ARTERIES


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Abstract

1. The selectivity of ω-conotoxin GVIA (ω-CTX) for prejunctional N-type voltage-operated calcium channels (VOCC) was examined in rat isolated small mesenteric arteries mounted in a Mulvany-Halpern myograph. Contractile responses to perivascular nerve stimulation, noradrenaline (NA) and potassium (K+) were obtained before and after treatment withω-CTX. The effects of ω-CTX were compared with those of felodipine, an L-type VOCC blocker.2. ω-CTX (3 nmol/L-10 µmol/L) inhibited contractions to electrical field stimulation by up to 94%, compared with the corresponding time control group. Felodipine (0.1 µmol/L) had little effect on the contractions to electrical stimulation compared with the vehicle-treated vessels.3. Concentration-response curves to exogenous NA (0.1-30 µmol/L) and contractions to a submaximal concentration of K+ (50 mmol/L) were unaffected by ω-CTX (3 nmol/L-10 µmol/L). In contrast, the maximum contraction to NA in vessels exposed to felodipine (0.1 µmol/L) was reduced by 37%, and the contraction to K+ (62 mmol/L) was reduced by 84% compared with vehicle-treated arteries.4. The results indicate that even at concentrations up to 10 µmol/L(10 000-fold higher than required to inhibit prejunctional N-type VOCC),ω-CTX inhibits only neurotransmitter release. Its effects are clearly different to felodipine as ω-CTX has no effect on post-junctionalα1-adrenoceptor-mediated vasoconstriction or direct smooth muscle depolarization considered to be mediated by L-type VOCC. Therefore, at least at the vascular neuroeffector junction, ω-CTX appears to be highly selective for N-type VOCC with no effect on L-type VOCC.

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