Noradrenaline modulation of calcium channels in single smooth muscle cells from rabbit ear artery.
1. Whole-cell recordings of voltage-gated Ca2+ current in single smooth muscle cells from rabbit ear artery were obtained with 110 mM-Ba2+ as charge carrier. 2. Noradrenaline (NA, 1-20 microM) produced a sustained increase in the dihydropyridine-sensitive L-type Ca2+ current, ranging up to 3-fold in some cells. The dihydropyridine-resistant T-type Ca2+ current was not affected. 3. The time and voltage dependence of activation and inactivation of the L-type current were not significantly changed during NA modulation. 4. The NA-induced increase in L-current was enhanced in magnitude and consistency by the inclusion of 200 microM-GTP in the pipette (internal) solution. 5. The effect of NA on L-current was not abolished by pre-treatment with prazosin, phentolamine or propranolol, suggesting that it is not mediated by alpha- or beta-adrenoceptors. 6. Phenylephrine (5 microM) was ineffective as an agonist, while adrenaline was approximately equipotent to NA. In these respects, the pharmacology of L-current modulation resembles that of 'gamma'-adrenergic receptors (Hirst & Nield, 1980). 7. NA modulation of L-type Ca2+ channels may be particularly important in promoting sympathetic vasoconstriction in resistance vessels where Ca2+ stores are relatively poorly developed and where NA-evoked contractions are very sensitive to organic Ca2+ channel antagonists.
Benham
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CD
Department of Physiology, Yale University School of Medicine, New Haven, CT 06510.
Tsien
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RW
D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D006160:Guanosine Triphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000502:physiology
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D011941:Receptors, Adrenergic; D010656:Phenylephrine; C038806:1,4-dihydropyridine; D006160:Guanosine Triphosphate; D009638:Norepinephrine