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(Circulation Research. 1999;85:596-605.)
© 1999 American Heart Association, Inc.

Cellular Biology

Predominant Distribution of Nifedipine-Insensitive, High Voltage–Activated Ca²⁺ Channels in the Terminal Mesenteric Artery of Guinea Pig

Hiromitsu Morita¹, Helen Cousins¹, Hitoshi Onoue, Yushi Ito, Ryuji Inoue

From the Department of Pharmacology (H.O., Y.I., R.I.), Graduate School of Medical Sciences, Kyushu University, and Special Patient Oral Care Unit (H.M.), Kyushu University Dental Hospital, Fukuoka, Japan, and Prince of Wales Medical Research Institute (H.C.), New South Wales, Australia.

Correspondence to Ryuji Inoue, Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. E-mail inouery{at}pharmaco.med.kyushu-u.ac.jp

Abstract—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 global I_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 -conotoxins GVIA and MVIIC (each 1 µmol/L) and -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 _1E 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.

Key Words: voltage-dependent Ca²⁺ channel • dihydropyridine insensitivity • arteriole • tone regulation

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