Dihydropyridine-sensitive single calcium channels in airway smooth muscle cells.
We have identified and characterized single voltage-dependent calcium channels in both acutely dissociated rat bronchial and cultured human tracheobronchial smooth muscle cells using the patch-clamp technique. In both cell types, on-cell membrane patches displayed unitary currents selective for barium ions and exhibited one conductance level (21-26 pS), and the open state probability was increased by membrane depolarization. Unitary barium currents were enhanced by the calcium channel selective agonist, BAY R 5417, and inhibited by the dihydropyridine calcium channel antagonist, nisoldipine (apparent inhibition constant less than 100 nM). Moreover, the degree of nisoldipine inhibition of the rat bronchial smooth muscle channels was increased with membrane depolarization in a manner consistent with the drug interacting with highest affinity to the inactivated channel state. In addition, the sensitivity to BAY R 5417 augmentation and nisoldipine inhibition of depolarization-induced tonic force of intact rat bronchial ring segments was in close agreement to the single channel results. Thus these data suggest that activation of voltage-dependent calcium channels can influence airway contraction and that dihydropyridines may be effective modulators of depolarization-induced increases in bronchial tone. We conclude that both rat and human airway smooth muscle cells have high-conductance voltage-dependent calcium channels that interact in a predictable manner with dihydropyridines and are similar to voltage-dependent calcium channels observed in other smooth muscle cells.
Worley
J F
JF
Department of Pharmacology and Toxicology, West Virginia University Health Sciences Center, Morgantown 26506.
Kotlikoff
M I
MI
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D001980:Bronchi / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002469:Cell Separation / Q000379:methods; D004553:Electric Conductivity; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology*; D015737:Nisoldipine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D015737:Nisoldipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011188:Potassium