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

Abstract

Abstract —We have found nifedipine-insensitive (NI), rapidly inactivating, voltage-dependent Ca 2+ 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 global I Ca in its periphery. With 5 mmol/L Ba 2+ 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 Ca 2+ -dependent inactivation, and exhibited the pore properties typical for high voltage–activated Ca 2+ channels; Ba 2+ is ≈2-fold more permeable than Ca 2+ , and Cd 2+ is a better blocker than Ni 2+ (IC 50 , 6 and 68 μmol/L, respectively). Relatively specific blockers for N- and P/Q-type Ca 2+ 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; IC 50 ; 107 μmol/L) blocked the current. Although these properties are reminiscent of R-type Ca 2+ channels, expression of the α 1E mRNA was not detected using reverse transcriptase–polymerase chain reaction. These results strongly suggest the predominant presence of NI, high voltage–activated Ca 2+ channels with novel properties, which may be abundantly expressed in peripheral small arterioles and contribute to their tone regulation.