Journal ArticleDOI
Mechanism of calcium channel blockade by verapamil, D600, diltiazem and nitrendipine in single dialysed heart cells
TLDR
Organic inhibitors of calcium influx prevent outward as well as inward current through cardiac calcium channels but do not slow current activation, and organic drugs show varying degrees of use-dependent block.Abstract:
Organic inhibitors of calcium influx prevent outward as well as inward current through cardiac calcium channels but do not slow current activation. Although block is antagonized by raising external calcium or barium concentrations, the competitive effect of permeant cations does not occur at the same cation binding site at which inorganic blockers act. Organic drugs show varying degrees of use-dependent block, due in part to blockade of open channels. Nitrendipine blockade of calcium currents requires doses >100-fold higher than expected from radioligand binding to isolated membranes.read more
Citations
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Journal ArticleDOI
Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists
TL;DR: The dihydropyridine Ca agonist Bay K 8644 enhances Ca channel current by promoting mode 2, while the Ca antagonists nitrendipine and nimodipine inhibit the current by favouring mode 0.
Journal ArticleDOI
Dominant role of N-type Ca2+ channels in evoked release of norepinephrine from sympathetic neurons.
Lane D. Hirning,A P Fox,Edwin W. McCleskey,Edwin W. McCleskey,Baldomero M. Olivera,Stanley A. Thayer,Richard J. Miller,Richard W. Tsien +7 more
TL;DR: N-type calcium channels play a dominant role in the depolarization-evoked release of norepinephrine, and are involved in stimulus-secretion coupling.
Journal ArticleDOI
Non-selective conductance in calcium channels of frog muscle: calcium selectivity in a single-file pore.
TL;DR: It is concluded that the selective permeability of Ca2+ channels depends on the presence of Ca3+ and Membrane currents in Ba2+/Ca2+ mixtures show anomalous mole‐fraction behaviour, suggesting that Ca2- channels are single‐file, multi‐ion pores.
Journal ArticleDOI
Antiarrhythmic Agents: The Modulated Receptor Mechanism of Action of Sodium and Calcium Channel-Blocking Drugs
L M Hondeghem,B G Katzung +1 more
TL;DR: This review concentrates on the antiarrhythmic drug literature pertinent to an evaluation of the modulated receptor hypothesis: lidocaine, procainamide, quinidine, diphenylhydantoin, and propranolol.
Journal ArticleDOI
Sodium current-induced release of calcium from cardiac sarcoplasmic reticulum
Normand Leblanc,Joseph R. Hume +1 more
TL;DR: In response to a transient rise of intracellular sodium, sodium-calcium exchange may promote calcium entry into cardiac cells and trigger sarcoplasmic calcium release during physiologic action potentials.
References
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Journal ArticleDOI
Specific Pharmacology of Calcium in Myocardium, Cardiac Pacemakers, and Vascular Smooth Muscle
TL;DR: In a wide variety of excitable cells the transmembrane exchange of the monovalent marine cations Na and K can be considered the substantial basis of bioelectric membrane activity, whereas Ca ions are required as mediators when, by this superfi cial process, intracellular reactions such as muscular contraction, glandular secre tion, or liberation of transmitter substances are initiated.
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Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction.
TL;DR: The results are interpreted in terms of a single receptor in Na channels for the different drug types, and any drug form in the channel increases the probability of closing the inactivation gate which, in effect, is equivalent to a negative shift of the voltage dependence of inactivation.
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Time- and voltage-dependent interactions of antiarrhythmic drugs with cardiac sodium channels.
TL;DR: A molecular model on the action of local anesthetic-like antiarrhytmic drugs is formulated: the drugs can interact with the sodium channels in the rested, activated and inactivated states, and each of these interactions is characterized by an association and dissociation rate constant.
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Comparative pharmacology of calcium antagonists: Nifedipine, verapamil and diltiazem
TL;DR: Nifedipine is a potent, long-acting vasodilator that has proved highly efficacious in relieving anginal symptoms caused by coronary vasospasm, and its value as an antiarrhythmic agent remains to be delineated.
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Differentiation of the transmembrane Na and Ca channels in mammalian cardiac fibres by the use of specific inhibitors
TL;DR: Verapamil and D 600 differ in this respect from common local anesthetic compounds such as xylocaine (lidocaine) or procaine which interfere much more with the transmembrane Na conductivity than with the Ca conductivity.