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

1 The possible involvement of pre-junctional non-N-type Ca2+ channels in no radrenaline (NA)mediated neurogenic contraction by electrical field stimula tion (EFS) was examined pharmaco-mechanically in the isolated rat mesenteri c artery. 2 EFS-generated contraction of endothelium-denuded mesenteric artery was fr equency-dependent (2-32 Hz) and was abolished by tetrodotoxin (TTX, 1 mu M) , guanethidine (5 mu M) or prazosin (100 nM), indicating that NA released f rom sympathetic nerve endings mediates the contractile response. 3 NA-mediated neurogenic contractions to lower frequency stimulations (2-8 Hz) were almost abolished by an N-type Ca2+ channel blocker, omega-conotoxi n-GVIA (1 mu M) whereas the responses to higher frequency stimulations (12- 32 Hz) were less sensitive to w-conotoxin-GVIA. The omega-conotoxin-GVIA-re sistant component of the contractile response to 32 Hz stimulation was inhi bited partly (10-20%) by omega-agatoxin-IVA (10-100 nM; concentrations whic h are relatively selective for P-type channels) and to a greater extent by omega-agatoxin-IVA (1 mu M) and omega-conotoxin-MVIIC (3 mu M), both of whi ch block Q-type channels at the concentrations used. 4 omega-Agatoxin-IVA (10-100 nM) alone inhibited 32 Hz EFS-induced contract ion by 10 similar to 20% whereas omega-conotoxin-MVIIC (3 mu M) alone inhib ited the response by similar to 60%. 5 These omega-toxin treatments did not affect the contractions evoked by ex ogenously applied NA. 6. These findings show that P- and Q-type as well as N-type Ca2+ channels a re involved in the sympathetic neurogenic vascular contraction, and suggest the significant role of non-N-type Ca2+ channels in NA release from adrene rgic nerve endings when higher frequency stimulations are applied to the ne rve.