The dihydropyridine niguldipine modulates calcium and potassium currents in vascular smooth muscle cells.
1. Vascular smooth muscle cells were isolated from the portal vein and from pial vessels of the cow. They were voltage-clamped with a single patch electrode technique (whole cell recording) in order to analyse the effects of niguldipine on ionic membrane currents. Due to adsorption of niguldipine to plastic and glass, the effective concentrations are lower than the nominal concentrations by a factor of about 3. 2. Niguldipine reduced Ca-currents (ICa of the L-type, voltage operated) at nominal concentrations greater than 0.1 microM up to a complete block at 1 microM (50% block at 0.4 microM). Nominal concentrations between 50 and 200 nM facilitated ICa ('Ca-agonistic effect'). The Ca-agonistic effects of niguldipine showed modest use- but strong voltage-dependence. 3. Niguldipine increased the outward currents at nominal concentrations greater than 10 nM. The extra outward currents reversed at -85 mV, the result suggesting that niguldipine had increased potassium currents, IK. Maximal facilitation of IK by niguldipine was about 400% and was obtained at 1 microM, half-maximal facilitation was obtained with a nominal concentration of 20 nM. 4. Both reduction of ICa and facilitation of IK may contribute to vasodilatation by niguldipine. Due to its greater sensitivity, the effects on IK may dominate.
Klöckner
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U
Department of Applied Physiology, University of Cologne, Köln, F.R.G.
Isenberg
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G
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D002550:Cerebral Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011169:Portal Vein / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D015221:Potassium Channels; D002118:Calcium; C054074:niguldipine