Contribution of nifedipine-insensitive voltage-dependent Ca2+ channel to diameter regulation in rabbit mesenteric artery.
We investigated a possible role of nifedipine-insensitive high voltage-activated (NI-HVA) Ca2+ channels in arterial diameter regulation in the semi-terminal branches of rabbit mesenteric artery (RMA). From these branches, NI-HVA Ca2+ currents showing almost identical properties to those previously identified in a similar region of guinea-pig [Circulation Research 1999;85:596-605] were recorded with whole-cell patch clamp recording. With video-microscopic measurement, the diameter of RMA segments perfused intraluminally at a constant rate (2-6 mL/h; 269 +/- 9 micro m, n = 27) decreased by 50-60% by raising the external K+ concentration ([K+]o) to 75 mM, a substantial part of which remained after addition of 1-10 micro M nifedipine (44 +/- 5% of initial diameter, n = 27). This nifedipine-insensitive diameter decrease (NI-DD) appeared to consist of initial transient and subsequent tonic phases (this separation was, however, not always clear), was resistant to tetrodotoxin, and was completely abolished in Ca2+-free or 100 micro M Cd2+-containing bath solutions. The magnitude of NI-DD increased depending on [K+]o with a threshold concentration of 20-40 mM. Raising the external Ca2+ concentration dose-dependently increased the magnitude of NI-DD, the extent being more prominent in the late tonic phase. Combined application of caffeine (10 mM) with ryanodine (3 micro M) produced a large transient NI-DD, which strongly attenuated the NI-DD evoked by a subsequent elevation in [K+]o. Using the fura-2 spectrofluorimetric Ca2+ imaging technique, a nifedipine-insensitive [Ca2+]i increase showing similar [K+]o-dependence and Cd2+ sensitivity to NI-DD was observed. These properties of NI-DD accord with those of NI-HVA Ca2+ channels, thus suggesting their contribution to small arterial diameter regulation in RMA.
Itonaga
Yasuhiro
Y
Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan
Nakajima
Tadasu
T
Morita
Hiromitsu
H
Hanano
Toyohisa
T
Miyauchi
Yuji
Y
Ito
Yushi
Y
Inoue
Ryuji
R
D000465:Algorithms; D000818:Animals; D001160:Arterioles / Q000033:anatomy & histology / Q000187:drug effects; D002104:Cadmium / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004594:Electrophysiology; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects*; D018715:Microscopy, Video; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011817:Rabbits; D013779:Tetrodotoxin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D005456:Fluorescent Dyes; D002104:Cadmium; D002110:Caffeine; D013779:Tetrodotoxin; D009543:Nifedipine; D002118:Calcium