American Journal of Physiology-Heart and Circulatory Physiology · 2002 · 59 citations · 24 references
Life SciencesPharmacologyPhysiologyIon Channel BiophysicsPharmacodynamicsSignal TransductionCalcium SignalingIon Channel ExpressionIon Channel PharmacologyIon Channel PhysiologyIon ChannelsMuscle PhysiologyCalcium Channel ConductanceCalcium Channel FunctionCalcium Channel PharmacologyCalcium Channel PhysiologyCalcium Ion SignalingChannelsL-type Calcium CurrentVoltage-gated Calcium Channels
T-type calcium channels may be involved in the maintenance of myogenic tone. We tested their role in isolated rat cremaster arterioles obtained after CO(2) anesthesia and decapitation. Total RNA was analyzed by RT-PCR and Southern blotting for calcium channel expression. We observed expression of voltage-operated calcium (Ca(V)) channels Ca(V)3.1 (T-type), Ca(V)3.2 (T-type), and Ca(V)1.2 (L-type) in cremaster arterioles (n = 3 rats). Amplification products were observed only in the presence of reverse transcriptase and cDNA. Concentration-response curves of the relatively specific L-type blocker verapamil and the relatively specific T-type blockers mibefradil and nickel were made on cannulated vessels with either myogenic tone (75 mmHg) or a similar level of constriction induced by 30 mM K(+) at 35 mmHg. Mibefradil and nickel were, respectively, 162-fold and 300-fold more potent in inhibiting myogenic tone compared with K(+)-induced constriction [log(IC(50), M): mibefradil, basal -7.3 +/- 0.2 (n = 9) and K(+) -5.1 +/- 0.1 (n = 5); nickel, basal -4.1 +/- 0.2 (n = 5) and K(+) -1.6 +/- 0.5 (n = 5); means +/- SE]. Verapamil had a 17-fold more potent effect [log(IC(50), M): basal -6.6 +/- 0.1 (n = 5); K(+) -5.4 +/- 0.3 (n = 4); all log(IC(50)) P < 0.05, basal vs. K(+)]. These data suggest that T-type calcium channels are expressed and involved in maintenance of myogenic tone in rat cremaster muscle arterioles.
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Selective inhibition of T-type Ca2+ channels by Ro 40-5967.
Santosh Kumar Mishra, Kent Hermsmeyer · Circulation Research · 1994 · 370 citations
Medicine, Biophysics, Pharmacology +14