Declining into failure - The age-dependent loss of the L-type calcium channel within the sinoatrial node

Article

关键词: SICK SINUS SYNDROME;    GAP JUNCTION PROTEIN;    HUMAN ATRIAL-FIBRILLATION;    SPATIAL-DISTRIBUTION;    CONDUCTION SYSTEM;    CA2+;    CURRENTS;    POTENTIALS;    EXPRESSION;    CONNEXIN43;   

DOI  :  10.1161/CIRCULATIONAHA.106.663070

来源: SCIE

【 摘 要 】

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(v)1.2 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(v)1.2 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(v)1.2-labeled protein progressively increased from 2.06 +/- 0.1 (mean +/- SEM) mm(2) at 1 month to 18.72 +/- 2.2 mm(2) at 38 months (P < 0.001). Western blot provided verification that Ca(v)1.2 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 mu mol/L nifedipine at 1 day old, compared with 30 mu mol/L at 1 month and 10 mu mol/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(v)1.2 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.

【 授权许可】

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