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

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 al 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 (4 = 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.