Effects on L-type calcium current of agents interfering with the cytoskeleton of isolated guinea-pig ventricular myocytes

We studied the effects of an external acute 10 min application of cytoskele tal interfering agents on cardiac L-type calcium current (I-Ca,I-L). We fou nd that colchicine, taxol and cytochalasin D had no direct effect on the L- type calcium channel as indicated by the absence of effect on voltage-depen dent parameters. Phalloidin induced a shift in the I-V curve which renders it difficult to use in excitation-contraction coupling studies. Microfilame nts of actin did not seem to regulate cardiac I-Ca,I-L as indicated by the lack of effect of cytochalasin D on I-Ca,I-L amplitude and inactivation kin etics. On the contrary, microtubules seem to be involved in the calcium-dep endent inactivation of I-Ca,I-L. This involvement might be direct, i.e. a p hysical link between the microtubules and some part of the channel protein, or it could be indirect, i.e. the calcium chelating properties and physica l obstacle of microtubules in the space between the sarcolemma and the SR.