title: Mechanisms underlying enhanced cardiac excitation contraction coupling observed in the senescent sheep myocardium.
abstract: Ageing related stiffening of the vascular system is believed to be in part responsible for a number of clinical outcomes including hypertension and heart failure. In the present study, we sought to determine whether there are alterations in cardiac excitation contraction coupling that may help compensate for the increased vessel stiffness. Experiments were performed on single cardiac myocytes isolated from young (18 months) and aged (>8 years) sheep. Intracellular Ca(2+) concentration, action potentials, L-type Ca(2+) currents and SR Ca(2+) content were measured at 23 degrees C. With ageing, cell capacitance increased by 26% indicating cellular hypertrophy. Action potential duration (APD90) (590 +/- 21 vs. 726 +/- 36 ms), Ca(2+) transient amplitude (112 +/- 15 vs. 202 +/- 25 nmol l(-1)) and fractional cell shortening (by 37%) also increased in the aged hearts (all values P < 0.05). The larger Ca(2+) transient amplitude observed under current clamp conditions was maintained under voltage clamp control; however, SR Ca(2+) content was identical. Both the peak L-type Ca(2+) current (2.8 +/- 0.3 vs. 4.9 +/- 0.5 pA pF(-1)) and integrated Ca(2+) entry (5.1 +/- 0.7 vs. 7.9 +/- 0.8 micromol l(-1), all P < 0.01) were greater in aged cells. In this study we show that in the ageing ovine myocardium, the amplitude of the systolic Ca(2+) transient is increased. The larger Ca(2+) transients cannot simply be explained by changes in APD and we suggest that the greater inward L-type Ca(2+) current provides a more effective trigger for calcium-induced-calcium release from the SR whilst maintaining a stable SR Ca(2+) content. These changes in cardiac excitation contraction coupling may help maintain cardiac output in the face of increased great vessel stiffness.
authors.affiliation: Unit of Cardiac Physiology, The University of Manchester, Manchester M13 9PT, UK.
authors.forename: K M
authors.initials: KM
authors.lastname: Dibb
authors.forename: U
authors.initials: U
authors.lastname: Rueckschloss
authors.forename: D A
authors.initials: DA
authors.lastname: Eisner
authors.forename: G
authors.initials: G
authors.lastname: Isenberg
authors.forename: A W
authors.initials: AW
authors.lastname: Trafford
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012756:Sheep / Q000378:metabolism*
chemical_list: D020746:Calcium Channels, L-Type; D002118:Calcium