H. Morita et al., Predominant distribution of nifedipine-insensitive, high voltage-activatedCa2+ channels in the terminal mesenteric artery of guinea pig, CIRCUL RES, 85(7), 1999, pp. 596-605
We have found nifedipine-insensitive (NI), rapidly inactivating, voltage-de
pendent Ca2+ channels (current, NI-I-Ca) with unique biophysical and pharma
cological properties in the terminal branches of guinea pig mesenteric arte
ry, by using a whole-cell mode of the patch-clamp technique. The fraction o
f NI-I-Ca appeared to increase dramatically along the lower branches of mes
enteric artery, amounting to almost 100% of global I-Ca in its periphery, W
ith 5 mmol/L Ba2+ as the charge carrier, NI-I-Ca was activated with a thres
hold 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 act
ivation near the resting membrane potential. The NI-I-Ca was rundown resist
ant, was not subject to Ca2+-dependent inactivation, and exhibited the pore
properties typical for high voltage-activated Ca2+ channels; Ba2+ is appro
ximate to 2-fold more permeable than Ca2+, and Cd2+ is a better blocker tha
n Ni2+ (IC50, 6 and 68 mu mol/L, respectively), Relatively specific blocker
s for N- and P/Q-type Ca2+ channels such as omega-conotoxins GVIA and MVIIC
(each 1 mu mol/L) and omega-agatoxin IVA (1 mu mol/L) were ineffective at
inhibiting NI-I-Ca, whereas nimodipine partially (10 mu mol/L; approximate
to 40%) and amiloride potently (approximate to 75% with 1 mmol/L; IC50; 107
mu mol/L) blocked the current. Although these properties are reminiscent o
f R-type Ca2+ channels, expression of the alpha(1E) mRNA was not detected u
sing reverse transcriptase-polymerase chain reaction. These results strongl
y suggest the predominant presence of NI, high voltage-activated Ca2+ chann
els with novel properties, which may be abundantly expressed in peripheral
small arterioles and contribute to their tone regulation.