Predominant distribution of nifedipine-insensitive, high voltage-activated Ca2+ 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 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 Ca(2+)-dependent inactivation, and exhibited the pore properties typical for high voltage-activated Ca2+ channels; Ba2+ is approximately 2-fold more permeable than Ca2+, and Cd2+ is a better blocker than Ni2+ (IC(50), 6 and 68 micromol/L, respectively). Relatively specific blockers for N- and P/Q-type Ca2+ channels such as omega-conotoxins GVIA and MVIIC (each 1 micromol/L) and omega-agatoxin IVA (1 micromol/L) were ineffective at inhibiting NI-I(Ca), whereas nimodipine partially (10 micromol/L; approximately 40%) and amiloride potently ( approximately 75% with 1 mmol/L; IC(50); 107 micromol/L) blocked the current. Although these properties are reminiscent of R-type Ca2+ channels, expression of the alpha(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.
Morita
H
H
Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, and Special Patient Oral Care Unit, Kyushu University Dental Hospital, Fukuoka, Japan.
Cousins
H
H
Onoue
H
H
Ito
Y
Y
Inoue
R
R
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D002413:Cations, Divalent / Q000378:metabolism; D004351:Drug Resistance; D004553:Electric Conductivity; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002413:Cations, Divalent; D009543:Nifedipine