title: Microtubule disruption modulates Ca(2+) signaling in rat cardiac myocytes.
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 micromol/L colchicine on calcium currents (I(Ca)) and [Ca(2+)](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). [Ca(2+)](i) transients were analyzed by fluo-3 epifluorescence simultaneously with I(Ca). Peak [Ca(2+)](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 micromol/L isoproterenol increased both I(Ca) and [Ca(2+)](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 micromol/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 [Ca(2+)](i) transient.
authors.affiliation: Physiopathologie Cardiovasculaire, INSERM U-390, Montpellier, France.
authors.forename: A M
authors.initials: AM
authors.lastname: Gómez
authors.forename: B G
authors.initials: BG
authors.lastname: Kerfant
authors.forename: G
authors.initials: G
authors.lastname: Vassort
mesh_terms: D000249:Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000502:physiology; D007425:Intracellular Membranes / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D000249:Adenosine Monophosphate; D007545:Isoproterenol; D017239:Paclitaxel; D002118:Calcium