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

We have found nifedipine-insensitive (NI), rapidly inactivating, voltage-dependent Ca 21 ch nnels (current, NI-ICa) 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 NIICa appeared to increase dramatically along the lower branches of mesenteric artery, amounting to almost 100% of global ICa in its periphery. With 5 mmol/L Ba 21 as the charge carrier, NIICa was activated with a threshold of 250 mV, peaked at 210 mV, and was half-activated and inactivated at211 and252 mV, respectively, generating a potential range of constant activation near the resting membrane potential. The NIICa was rundown resistant, was not subject to Ca -dependent inactivation, and exhibited the pore properties typical for high voltage–activated Ca 21 channels; Ba 21 is '2-fold more permeable than Ca , and Cd is a better blocker than Ni 21 (IC50, 6 and 68mmol/L, respectively). Relatively specific blockers for Nand P/Q-type Ca channels such as v-conotoxins GVIA and MVIIC (each 1mmol/L) and v-agatoxin IVA (1 mmol/L) were ineffective at inhibiting NI-I Ca, whereas nimodipine partially (10 mmol/L; '40%) and amiloride potently ('75% with 1 mmol/L; IC50; 107mmol/L) blocked the current. Although these properties are reminiscent of R-type Ca 21 ch nnels, expression of thea1E mRNA was not detected using reverse transcriptase–polymerase chain reaction. These results strongly suggest the predominant presence of NI, high voltage–activated Ca 21 channels with novel properties, which may be abundantly expressed in peripheral small arterioles and contribute to their tone regulation. (Circ Res. 1999;85:596-605.)