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(Circulation. 2007;115:1183-1190.)
© 2007 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Declining Into Failure

The Age-Dependent Loss of the L-Type Calcium Channel Within the Sinoatrial Node

Sandra A. Jones, PhD; Mark R. Boyett, PhD; Matthew K. Lancaster, PhD

From the Institute of Membrane and Systems Biology (S.A.J., M.K.L.), Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom, and School of Medicine (M.R.B.), University of Manchester, Manchester, United Kingdom.

Correspondence to Dr Sandra A. Jones, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom. E-mail s.a.jones{at}leeds.ac.uk

Received September 6, 2006; accepted December 15, 2006.

Background— The spontaneous activity of pacemaker cells in the sinoatrial (SA) node controls heart rate under normal physiological conditions. Clinical studies have shown the incidence of SA node dysfunction increases with age and occurs with peak prevalence in the elderly population. The present study investigated whether aging affected the expression of Ca_v1.2 channels and whether these changes could affect pacemaker activity, in turn leading to age-related SA node degeneration.

Methods and Results— The SA node region was isolated from the right atrium of guinea pigs between birth and 38 months of age. Immunofluorescence studies showed Ca_v1.2 protein was present as punctate labeling around the outer membrane of atrial cells but was absent from the center of the SA node. The area lacking Ca_v1.2-labeled protein progressively increased from 2.06±0.1 (mean±SEM) mm² at 1 month to 18.72±2.2 mm² at 38 months (P<0.001). Western blot provided verification that Ca_v1.2 protein expression within the SA node declined during aging. Functional measurements showed an increased sensitivity to the L-type calcium blocker nifedipine; SA node preparations stopped beating in 100 µmol/L nifedipine at 1 day old, compared with 30 µmol/L at 1 month and 10 µmol/L at 38 months of age. Furthermore, the amplitude of extracellular potentials declined within the center and periphery of the SA node during aging.

Conclusions— The present data show Ca_v1.2 channel protein decreases concurrently with reduced spontaneous activity of the SA node with increased age, which provides further evidence of mechanisms underlying the age-related deterioration of the cardiac pacemaker.

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