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(Circulation Research. 2000;86:30.)
© 2000 American Heart Association, Inc.

Cellular Biology

Microtubule Disruption Modulates Ca²⁺ Signaling in Rat Cardiac Myocytes

A. M. Gómez, B. G. Kerfant, G. Vassort

From Physiopathologie Cardiovasculaire, INSERM U-390, Montpellier, France.

Correspondence to Ana M. Gómez, INSERM U-390, CHU Arnaud de Villeneuve, 34295 Montpellier, France. E-mail agomez{at}u390.montp.inserm.fr

Abstract—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 µmol/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 fluo-3 epifluorescence simultaneously with I_Ca. Peak [Ca²⁺]_i transients were significantly increased in cardiac myocytes treated with colchicine. The values of F/F₀ 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). ß-Adrenergic stimulation with 1 µmol/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 µmol/L 2'-deoxyadenosine 3'-monophosphate blunted the colchicine effect. We suggest that ß-adrenergic stimulation and microtubule disruption share a common pathway to enhance I_Ca and [Ca²⁺]_i transient.

Key Words: heart • Ca²⁺ current • microtubule • Ca²⁺ transient • ß-adrenergic stimulation

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