T-channel-like pharmacological properties of high voltage-activated, nifedipine-insensitive Ca2+ currents in the rat terminal mesenteric artery

1. Pharmacological properties of nifedipine-insensitive, high voltage-activated Ca(2+) channels in rat mesenteric terminal arteries (NICCs) were investigated and compared with those of alpha1E and alpha1G heterologously expressed in BHK and HEK293 cells respectively, using the patch clamp technique. 2. With 10 mM Ba(2+) as the charge carrier, rat NICCs (unitary conductance: 11.5 pS with 110 mM Ba(2+)) are almost identical to those previously identified in a similar region of guinea-pig, such as in current-voltage relationship, voltage dependence of activation and inactivation, and divalent cation permeability. However, these properties are considerably different when compared with alpha1E and alpha1G. 3. SNX-482(200 nM and sFTX3.3 (1 micro M), in addition to omega-conotoxin GVIA (1 micro M) and omega-agatoxin IVA (100 nM), were totally ineffective for rat NICC currents, but significantly suppressed alpha1E (by 82% at 200 nM; IC(50)=11.1 nM) and alpha1G (by 20% at 1 micro M) channel currents, respectively. A non-specific T-type Ca(2+) channel blocker nimodipine (10 micro M) differentially suppressed these three currents (by 40, 3 and 85% for rat NICC, alpha1E and alpha1G currents, respectively). 4. Mibefradil, the widely used T-type channel blocker, almost equally inhibited rat NICC and alpha1G currents in a voltage-dependent fashion with similar IC(50) values (3.5 and 0.3 micro M and 2.4 and 0.14 micro M at -100 and -60 mV, respectively). Furthermore, other organic T-type channel blockers such as phenytoin, ethosuximide, an arylpiperidine derivative SUN N5030 (IC(50)=0.32 micro M at -60 mV for alpha1G) also exhibited comparable inhibitory efficacies for NICC currents (inhibited by 22% at 100 micro M; IC(50)=27.8 mM; IC(50)=0.53 micro M, respectively). 5. These results suggest that despite distinctive biophysical properties, the rat NICCs have indistinguishable pharmacological sensitivities to many organic blockers compared with T-type Ca(2+) channels.