Catecholamines and development of cardiac pacemaking: an intrinsically intimate relationship

A generation ago, a melding of imagination and experimental evidence led to the hypothesis that catecholamines were essential in establishing basal cardiac pacemaking rhythm. Subsequent discoveries of depolarizing "pacemaker" currents and viable adult catecholamine-deficient animals raised serious doubts about the necessity of catecholamines in pacemaking. However, the findings that catecholamines are produced in pacemaking regions prior to innervation, and that they are required for embryonic survival during a defined "critical period" of embryonic development have revitalized the original hypothesis. Recent results have further suggested that intrinsic cardiac adrenergic cells can differentiate into pacemaking myocytes, and that protein kinase A, a prominent downstream mediator of beta-adrenergic signaling, is required for pacemaking activity. Here, we discuss how catecholamines and the intrinsic cardiac adrenergic cells that produce them may influence ontological development of cardiac pacemaking.