Calcium currents, charge movement and dihydropyridine binding in fast- and slow-twitch muscles of rat and rabbit.
1. The Vaseline-gap technique was used to record slow calcium currents and asymmetric charge movement in single fibres of fast-twitch muscles (extensor digitorum longus (e.d.l.) and sternomastoid) and slow-twitch muscles (soleus) from rat and rabbit, at a holding potential of -90 mV. 2. The slow calcium current in soleus fibres was about one-third of the size of the current in e.d.l. fibres, but was very similar otherwise. In both e.d.l. and soleus fibres, the dihydropyridine (DHP), nifedipine, suppressed the calcium current entirely. 3. In these normally polarized fibres, nifedipine suppressed only part (qns) of the asymmetric charge movement. The proportion of qns suppressed by various concentrations of nifedipine was linearly related to the associated reduction of the calcium current. Half-maximal suppression of both parameters was obtained with about 0.5 microM-nifedipine. The calcium current and the qns component of the charge movement also were suppressed over the same time course by nifedipine. Another DHP calcium antagonist, (+)PN200/110, was indistinguishable from nifedipine in its effects of suppressing calcium currents and qns. 4. In all muscle types, the total amount of qns in each fibre was linearly related to the size of the calcium current (in the absence of DHP). On average, qns was 3.3 times larger in e.d.l. fibres than in soleus fibres. 5. In contrast to the other dihydropyridines, (-)bay K8644, a calcium channel agonist, did not suppress any asymmetric charge movement. 6. The potential dependence of the slow calcium current implied a minimum gating charge of about five or six electronic charges. The movement of qns occurred over a more negative potential range than the change in calcium conductance. 7. Experiments on the binding of (+)PN200/110 indicated that e.d.l. muscles had between about 2 and 3 times more specific DHP binding sites than did soleus muscle. 8. These results point to a close relationship between slow calcium channels, the qns component of the charge movement and DHP binding sites, in both fast- and slow-twitch mammalian muscle. qns appears to be part of the gating current of the T-system calcium channels.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004095:Dihydropyridines / Q000378:metabolism*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology*; D017275:Isradipine; D009132:Muscles / Q000378:metabolism / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D013997:Time Factors
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007473:Ion Channels; D010069:Oxadiazoles; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D002118:Calcium; D017275:Isradipine