Microtubule disruption modulates Ca2+ signaling in rat cardiac myocytes

Microtubules have been shown to alter contraction in cardiac myocytes throu gh changes in cellular stiffness. However, an effect on excitation-contract ion coupling has not been examined. Here we analyze the effects of microtub ule 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 wh ole-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 colchic ine-treated myocytes, respectively; P<0.05). I-Ca inactivation was well fit ted by a biexponential function. The slow component of inactivation was unc hanged, whereas the fast component was accelerated after colchicine treatme nt (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 epifl uorescence simultaneously with I-Ca. Peak [Ca2+](i) transients were signifi cantly 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 colch icine-treated cells (P<0.05). beta-Adrenergic stimulation with 1 mu mol/L i soproterenol increased both I-Ca and [Ca2+](i) transient in control cells. However, no significant change was induced by isoproterenol on colchicine-t reated cells. Colchicine and isoproterenol effects were similar and not add itive. Inhibition of adenylyl cyclase by 200 mu mol/L 2'-deoxyadenosine 3'- monophosphate blunted the colchicine effect. We suggest that beta-adrenergi c stimulation and microtubule disruption share a common pathway to enhance I-Ca and [Ca2+](i) transient.