Significant role of neuronal non‐N‐type calcium channels in the sympathetic neurogenic contraction of rat mesenteric artery

The possible involvement of pre‐junctional non‐N‐type Ca 2+ channels in noradrenaline (NA)‐mediated neurogenic contraction by electrical field stimulation (EFS) was examined pharmacomechanically in the isolated rat mesenteric artery. EFS‐generated contraction of endothelium‐denuded mesenteric artery was frequency‐dependent (2–32 Hz) and was abolished by tetrodotoxin (TTX, 1 μ M ), guanethidine (5 μM) or prazosin (100 n M ), indicating that NA released from sympathetic nerve endings mediates the contractile response. NA‐mediated neurogenic contractions to lower frequency stimulations (2–8 Hz) were almost abolished by an N‐type Ca 2+ channel blocker, ω‐conotoxin‐GVIA (1 μ M ) whereas the responses to higher frequency stimulations (12–32 Hz) were less sensitive to ω‐conotoxin‐GVIA. The ω‐conotoxin‐GVIA‐resistant component of the contractile response to 32 Hz stimulation was inhibited partly (10–20%) by ω‐agatoxin‐IVA (10–100 n M ; concentrations which are relatively selective for P‐type channels) and to a greater extent by ω‐agatoxin‐IVA (1 μ M ) and ω‐conotoxin‐MVIIC (3 μ M ), both of which block Q‐type channels at the concentrations used. ω‐Agatoxin‐IVA (10–100 n M ) alone inhibited 32 Hz EFS‐induced contraction by 10∼20% whereas ω‐conotoxin‐MVIIC (3 μ M ) alone inhibited the response by ∼60%. These ω‐toxin treatments did not affect the contractions evoked by exogenously applied NA. These findings show that P‐ and Q‐type as well as N‐type Ca 2+ channels are involved in the sympathetic neurogenic vascular contraction, and suggest the significant role of non‐N‐type Ca 2+ channels in NA release from adrenergic nerve endings when higher frequency stimulations are applied to the nerve.British Journal of Pharmacology (1999) 128 , 1602–1608; doi: 10.1038/sj.bjp.0702954