Age-related differences in excitation-contraction coupling in rat papillary muscle

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Abstract
To investigate the possible role of an alteration in excitation-contraction coupling during development, aging and senescence we compared simultaneously recorded mechanical and electrical activity of left ventricular papillary muscles from 3, 6, 12, and 24-month-old male rats. In addition, the effects of calcium and verapamil on excitation-contraction coupling were evaluated. We recorded transmembrane action potentials during both isometric and isotonic contractions. At an external bath calcium=2.4 mM, action potential duration at 75% complete repolarization (APD75) was significantly prolonged as a function of age (3 mo=28.2±2.7; 6 mo=29.5±2.6; 12 mo=49.5±5.6; 24 mo=121±8.5 msec) while peak developed tension (DT) was not significantly altered (3 mo=5.13±0.53; 6 mo=4.75±0.53; 12 mo=7.26±0.51; 24 mo=6.01±0.67 g/mm2). The correlation coefficient (r value) for APD75 and DT was strong for 3-month-old animals (r=0.99) but weakened as a function of age (6 mo=0.93; 12 mo=0.81; 24 mo=0.57). Similar results were observed when APD75 was correlated with time-to-peak tension (TPT) (3 mo=0.95; 6 mo=0.98; 12 mo=0.85; 24 mo=0.68), time-to-one-half relaxation (T1/2R) (3 mo=0.91; 6 mo=0.97; 12 mo=0.85; 24 mo=0.81) and time to peak shortening (TPS) (3 mo=0.89; 6 mo=0.81; 12 mo=0.82; 24 mo=0.51). Correlations between action potential duration and contractile parameters became weak in all age groups upon the addition of verapamil (V). The correlation between APD75 and DT for 3-month-old animals decreased by 34% upon the addition of V while a 70% decrease was seen in 24-month-old animals. Similar results were seen when APD75 was correlated with TPT, T1/2R and TPS when V was added to the perfusate. Our results indicate that excitation-contraction coupling, as evidence by alterations in not only the contractile apparatus but also in the surface membrane, may be altered in ventricular muscle as in function of age.