NALCN: A Regulator of Pacemaker Activity

Pacemaker cells play a fundamental role in generating or regulating many essential biological rhythms. Spontaneous pacemaker activity is dependent on the function of an array of ion channels expressed in these cells. Recent characterization of a Na(+) leak channel (NALCN) has linked to its role in conducting the background Na(+) current that depolarizes resting membrane properties of pacemaker neurons. NALCN, along with Unc79 and Unc80, forms a protein complex that is involved in regulating intrinsic membrane and synaptic activities. In this review, we will discuss the current understanding of NALCN channel physiology and its role in regulating cell excitability and pacemaker activity.