Alterations in properties of L-type Ca channels in aging rat heart

I. R. JOSEPHSON, A. GUIA, M. D. STERN AND E. G. LAKATTA. Alterations in Properties of L-Type Ca Channels in Aging Rat Heart. Journal of Molecular and Cellular Cardiology (2002) 34, 297-308. Previous studies of whole-cell L-type Ca currents in aging heart have demonstrated an increase in the peak Ca current magnitude in proportion to the increase in membrane area, and a slowing of the time course for inactivation. However, the single-channel mechanisms underlying this upregulation, and for the slowed inactivation are not known. We have therefore compared the properties of single L-type Ca channel currents recorded from ventricular myocytes obtained from young adult (3 month), adult (6-8 month) and aging (24 month) Wistar rats, using 5 mM Ba ions as the permeant ion. We report that the peak ensemble-averaged single Ca channel currents from aging heart (-280+/-57fA) were enhanced compared to those from young adult (-137+/-16fA), or adult hearts (-144 +/- 38 fA). This surprising result was related, in part, to an apparent increase in the number of active Ca channels per patch in aging (1.90+/-0.23) v young adult (1.33+/-0.19) or adult heart (1.50+/-0.2). Moreover, there was an increase in the time constant for inactivation of the ensemble-averaged Ca currents of aging (471+/-169ms), compared with young adult (198+/-43ms), or adult heart (196+/-32ms). The aging-related changes were also traced to alterations in single Ca channel gating, including an increase in the average probability of being open, and an increase in the availability of single Ca currents in aging heart. In contrast, the unitary Ca current amplitude was unchanged with aging. These novel findings suggest that the compensatory increase in the L-type Ca currents during aging is a consequence of an apparent increase in both the number, and the activity of individual L-type Ca channels. (C) 2002 Elsevier Science Ltd. All rights reserved.