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

Summary 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.Support in part by NIH Grants # HL 21933-04, # 07071-06 and a Herman Raucher Investigatorship Award of the New York Heart Association to Dr. Joseph M. Capasso. Animals used in this study were generously awarded to Dr. Capasso by the Animal Acquisitions Branch of the National Institute of Aging.