Beating rate of isolated neonatal cardiomyocytes is regulated by the stable microtubule subset

We investigated the roles of microtubule (MT) dynamics (growth and shrinkag e), the stable, nongrowing MT subset, the posttranslationally detyrosinated MT subset, and artificially elevated tubulin levels in the negative regula tion of heart cell beating rate. We manipulated the MT populations in isola ted, neonatal cardiomyocytes obtained from normal animals in several ways a nd then measured heart cell beating rate directly. We found that the stabil ized population of MTs was sufficient to maintain a normal beating rate, wh ereas MT dynamics and detyrosination made no observable contribution. Furth ermore, by directly and acutely increasing the level of tubulin within othe rwise normally beating cells, we found that the increased tubulin (and MT) levels further depressed the beating rate. In conclusion, the stabilized MT subset is sufficient to maintain the normal beating rate in these cells, w hereas increasing the MT density depresses it.