A Long-Term Blockade of L-Type Calcium Currents Upregulates the Number of Ca2+ Channels in Skeletal Muscle |
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Authors: | MC García JM Farías J Escamilla S Sánchez-Armass JA Sánchez |
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Institution: | (1) From the Department of Pharmacology, Centro de Investigación y de Estudios Avanzados del I.P.N., México D.F. 07300, México, MX;(2) Department of Physiology, Universidad Autónoma de San Luis Potosí, 78230, México, MX |
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Abstract: | The effects of a long-term blockade of L-type Ca2+ channels on membrane currents and on the number of dihydropyridine binding sites were investigated in skeletal muscle fibers.
Ca2+ currents (I
Ca) and intramembrane charge movement were monitored using a voltage-clamp technique. The peak amplitude of I
Ca increased by more than 40% in fibers that were previously incubated for 24 hr in solutions containing the organic Ca2+ channel blocker nifedipine or in Ca2+-free conditions. A similar incubation period with Cd2+, an inorganic blocker, produced a moderate increase of 20% in peak I
Ca. The maximum mobilized charge (Q
max) increased by 50% in fibers preincubated in Ca2+-free solutions or in the presence of Cd2+.
Microsomal preparations from frog skeletal muscle were isolated by differential centrifugation. Preincubation with Cd2+ prior to the isolation of the microsomal fraction doubled the number of 3H-PN200-110 binding sites and produced a similar increase in the values of the dissociation constant. The increase in the
number of binding sites is consistent with the increase in the peak amplitude of I
Ca as well as with the increase in Q
max.
Received: 31 August 1998/Revised: 7 December 1998 |
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Keywords: | : Ca2+ channels — DHP receptors — Upregulation — Skeletal muscle — Channel blockers |
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