Predominant Distribution of Nifedipine-Insensitive, High Voltage–Activated Ca 2+ Channels in the Terminal Mesenteric Artery of Guinea Pig

—We have found nifedipine-insensitive (NI), rapidly inactivating, voltage-dependent Ca2+ channels (current, NI-I Ca ) with unique biophysical and pharmacological properties in the terminal branches of guinea pig mesenteric artery, by using a whole-cell mode of the patch-clamp technique. The fraction of NI-I Ca appeared to increase dramatically along the lower branches of mesenteric artery, amounting to almost 100% of globalI Ca in its periphery. With 5 mmol/L Ba2+ as the charge carrier, NI-I Ca was activated with a threshold of −50 mV, peaked at −10 mV, and was half-activated and inactivated at −11 and −52 mV, respectively, generating a potential range of constant activation near the resting membrane potential. The NI-I Ca was rundown resistant, was not subject to Ca2+ -dependent inactivation, and exhibited the pore properties typical for high voltage–activated Ca2+ channels; Ba2+ is ≈2-fold more permeable than Ca2+ , and Cd2+ is a better blocker than Ni2+ (IC50 , 6 and 68 μmol/L, respectively). Relatively specific blockers for N- and P/Q-type Ca2+ channels such as ω-conotoxins GVIA and MVIIC (each 1 μmol/L) and ω-agatoxin IVA (1 μmol/L) were ineffective at inhibiting NI-I Ca , whereas nimodipine partially (10 μmol/L; ≈40%) and amiloride potently (≈75% with 1 mmol/L; IC50 ; 107 μmol/L) blocked the current. Although these properties are reminiscent of R-type Ca2+ channels, expression of the α1E mRNA was not detected using reverse transcriptase–polymerase chain reaction. These results strongly suggest the predominant presence of NI, high voltage–activated Ca2+ channels with novel properties, which may be abundantly expressed in peripheral small arterioles and contribute to their tone regulation.