title: Effects of aging on Ca2+ signaling in murine mesenteric arterial smooth muscle cells.
abstract: Pathophysiological changes in arterial smooth muscle structure and function occur with aging and there are a number of reports illustrating reductions in vascular responsiveness with aging. While much is known about arterial remodeling and functional adaptations with aging, very little is known about the biophysical adaptations in individual arterial myocytes. Cytosolic Ca2+ signaling, involving activation of L-type Ca2+ channels on the plasma membrane as well as InsP3 and ryanodine receptors on the sarcoplasmic reticulum, is integral to vascular tone and reactivity. Thus, we tested the hypothesis that aging results in reductions in the functional expression of L-type channels and temporal aspects of ryanodine receptor and InsP3 receptor Ca2+ signaling, in mesenteric arterial smooth muscle cells isolated from 6 and 30 months old C57Bl/6 mice. Comparisons of L-type current activity were made using dialyzed, whole-cell voltage-clamp techniques and Ba2+ as charge carrier. Ca2+ signaling was measured using fura-2 fluorescence microscopy techniques. Cell morphological changes were also investigated using electrophysiological and immunocytochemical approaches. The amplitudes of L-type Ca2+ currents were increased in older mice, but this was associated with membrane surface area increases of approximately 50%, due to increases in cell length not cell width. Consequently, L-type Ca2+ current densities were preserved with age, indicating functional channel expression was unchanged. In contrast, aging was associated with decrements in Ca2+ signaling in response to either ryanodine receptor stimulation by caffeine or InsP3 receptor activation with phenylephrine. These changes with aging may be related to the previously reported depression in myogenic reactivity.
authors.affiliation: Department of Physiology, University of Nevada School of Medicine, Reno, NV 89557, USA.
authors.forename: Cristiane
authors.initials: C
authors.lastname: del Corsso
authors.forename: Olga
authors.initials: O
authors.lastname: Ostrovskaya
authors.forename: Claire E
authors.initials: CE
authors.lastname: McAllister
authors.forename: Keith
authors.initials: K
authors.lastname: Murray
authors.forename: William J
authors.initials: WJ
authors.lastname: Hatton
authors.forename: Alison M
authors.initials: AM
authors.lastname: Gurney
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Spencer
authors.forename: Sean M
authors.initials: SM
authors.lastname: Wilson
mesh_terms: D000375:Aging; D000818:Animals; D001464:Barium / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002468:Cell Physiological Phenomena; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004594:Electrophysiology; D016257:Fura-2 / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008638:Mesenteric Arteries / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015233:Models, Statistical; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010656:Phenylephrine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D051036:Large-Conductance Calcium-Activated Potassium Channels; D019837:Ryanodine Receptor Calcium Release Channel; D010656:Phenylephrine; D001464:Barium; D002110:Caffeine; D002118:Calcium; D016257:Fura-2