Journal
CIRCULATION RESEARCH
Volume 86, Issue 1, Pages 30-36Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.RES.86.1.30
Keywords
heart; Ca2+ current; microtubule; Ca2+ transient; beta-adrenergic stimulation
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Microtubules have been shown to alter contraction in cardiac myocytes through changes in cellular stiffness. However, an effect on excitation-contraction coupling has not been examined. Here we analyze the effects of microtubule disruption by 1 mu mol/L colchicine on calcium currents (I-Ca) and [Ca2+](i) transients in rat ventricular myocytes. I-Ca was studied using the whole-cell patch-clamp technique. Colchicine treatment increased I-Ca density (peak values, -4.6+/-0.4 and -9.1+/-1.3 pA/pF in 11 control and 12 colchicine-treated myocytes, respectively; P<0.05). I-Ca inactivation was well fitted by a biexponential function. The slow component of inactivation was unchanged, whereas the fast component was accelerated after colchicine treatment (at -10 mV, 11.8+/-1.0 versus 6.7+/-1.0 ms in control versus colchicine-treated cells; P<0.005). [Ca2+](i) transients were analyzed by flue-3 epifluorescence simultaneously with I-Ca. Peak [Ca2+](i) transients were significantly increased in cardiac myocytes treated with colchicine. The values of F/F-0 at 0 mV were 1.1+/-0.02 in 9 control cells and 1.4+/-0.1 in 11 colchicine-treated cells (P<0.05). beta-Adrenergic stimulation with 1 mu mol/L isoproterenol increased both I-Ca and [Ca2+](i) transient in control cells. However, no significant change was induced by isoproterenol on colchicine-treated cells. Colchicine and isoproterenol effects were similar and not additive. Inhibition of adenylyl cyclase by 200 mu mol/L 2'-deoxyadenosine 3'-monophosphate blunted the colchicine effect. We suggest that beta-adrenergic stimulation and microtubule disruption share a common pathway to enhance I-Ca and [Ca2+](i) transient.
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