Human Biological Pacemakers: Intrinsic Variability and Stability
In healthy individuals, the sinoatrial node (SAN) is responsible for initiating excitation over 100,000 times per day. As with all cardiac pacemaking cells in the specialized conduction system, SAN automaticity is driven by diastolic depolarization via several redundant pathways to ensure that the heart beats. Key cellular mechanisms include the hyperpolarization-activated inward current If and the "Ca Clock" (inward Na/Ca exchange current activated by sarcoplasmic reticulum Ca2+ release).1 However, molecular, histological, electrophysiological, and in silico studies have revealed that the SAN is extremely complex and the redundant systems not only provide safety of pacemaking, but also allows for precise modulation of heart rate to accommodate changing physiological demands. Despite this ingenious design, physiological pacing can fail due to either SAN pathology or atrioventricular block, requiring implantation of an electronic pacemaker. (SELECT FULL TEXT TO CONTINUE)
- Received January 6, 2012.
- Accepted January 13, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited