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- Title
Depolarization-induced calcium influx in rat mesenteric small arterioles is mediated exclusively via mibefradil-sensitive calcium channels.
- Authors
Jensen, Lars J.; Salomonsson, Max; Jensen, Boye L.; Holstein-Rathlou, Niels-Henrik
- Abstract
1: In this study, intracellular Ca2+ was measured as the Fura-2 ratio (R) of fluorescence excited at 340 and 380?nm (F340/F380) in nonpressurized rat mesenteric small arterioles (\[emptyv] (lumen diameter) 10-25?µm). The response to depolarization using 75?mM KCl was an increase in R from a baseline of 0.96±0.01 ([Ca2+]i ~74?nM) to 1.04±0.01 (~128?nM) (n=80). 2: The response to 75?mM K+ was reversibly abolished in Ca2+-free physiological saline solution, whereas phentolamine (10?µM) or tetrodotoxin (1?µM) had no effects. LaCl3 (200?µM) inhibited 61±9% of the response. 3: A [K+]-response curve indicated that the Ca2+ response was activated between 15 and 25?mM K+. The data suggest that the Ca2+ response was caused by the activation of voltage-dependent Ca2+ channels. 4: Mibefradil use dependently inhibited the Ca2+ response to 75?mM K+ by 29±2% (100?nM), 73±7% (1?µM) or 89±7% (10?µM). Pimozide (500?nM) use dependently inhibited the Ca2+ response by 85±1%. 5: Nifedipine (1?µM) inhibited the Ca2+ response to 75?mM K+ by 41±12%. The response was not inhibited by calciseptine (500?nM), ?-agatoxin IVA (100?nM), ?-conotoxin MVIIA (500?nM), or SNX-482 (100?nM). 6: Using reverse transcriptase-polymerase chain reaction, it was shown that neither CaV2.1a (P-type) nor CaV2.1b (Q-type) voltage-dependent Ca2+ channels were expressed in mesenteric arterioles, whereas the CaV3.1 (T-type) channel was expressed. Furthermore, no amplification products were detected when using specific primers for the ß1b, ß2, or ß3 auxiliary subunits of high-voltage-activated Ca2+ channels. 7: The results suggest that the voltage-dependent Ca2+ channel activated by sustained depolarization in mesenteric arterioles does not classify as any of the high-voltage-activated channels (L-, P/Q-, N-, or R-type), but is likely to be a T-type channel. The possibility that the sustained Ca2+ influx observed was the result of a T-type window current is discussed.British Journal of Pharmacology (2004) 142, 709-718. doi:10.1038/sj.bjp.0705841
- Subjects
DENMARK; CALCIUM channels; MESENTERIC artery; CALCIUM in the body; ACTION potentials; VASCULAR smooth muscle; HEMODYNAMICS; BIOLOGICAL transport; CALCIUM metabolism; MESENTERIC artery physiology; SMOOTH muscle physiology; ANIMAL experimentation; ARTERIES; ARTHROPOD venom; CALCIUM; CARRIER proteins; CHEMICAL elements; COMPARATIVE studies; GENE expression; HETEROCYCLIC compounds; IMMUNOBLOTTING; LIGHT; MARINE toxins; RESEARCH methodology; MEDICAL cooperation; NIFEDIPINE; NUCLEOTIDE separation; PHENTOLAMINE; SNAKE venom; POLYMERASE chain reaction; POTASSIUM chloride; RATS; RESEARCH; SMOOTH muscle; SOLUTION (Chemistry); EVALUATION research; REVERSE transcriptase polymerase chain reaction; MIBEFRADIL (Drug); PHARMACODYNAMICS; ANATOMY; PHYSIOLOGY
- Publication
British Journal of Pharmacology, 2004, Vol 142, Issue 4, p709
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1038/sj.bjp.0705841