Pluripotent mouse embryonic stem cells are able to differentiate into cardiomyocytes expressing chronotropic responses to adrenergic and cholinergic agents and Ca2+ channel blockers

摘要: A defined cultivation system was developed for the differentiation of pluripotent embryonic stem cells mouse into spontaneously beating cardiomyocytes, allowing investigations chronotropic responses, as well electrophysiological studies different cardioactive drugs in vitro. The beta-adrenoceptor agonists (-)isoprenaline and clenbuterol, mediators cAMP metabolism, forskolin isobutylmethylxanthine (IBMX), alpha 1-adrenoceptor agonist (-)phenylephrine, heart glycoside digitoxin induced a positive, muscarinic cholinoceptor carbachol L-type Ca2+ channel blockers nisoldipine, gallopamil diltiazem negative response. In early differentiated cardiomyocytes beta 1-, but not 2-adrenoceptors, cholinoceptors, channels participated terminally 2-adrenoceptors responses were also functionally expressed. contractions concomitant with rhythmic action potentials very similar to those described sinus-node cells. We conclude that differentiating from are able develop adrenoceptors cholinoceptors signal transduction pathways consequence cell-cell interactions during embryoid body formation vitro, independent development living organisms. cellular may be useful vitro assay toxicological model studying commitment