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Enhanced L‐type Ca 2+ channel current density in coronary smooth muscle of exercise‐trained pigs is compensated to limit myoplasmic free Ca 2+ accumulation
Author(s) -
Heaps Cristine L.,
Bowles Douglas K.,
Sturek Michael,
Laughlin M. Harold,
Parker Janet L.
Publication year - 2000
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2000.00435.x
Subject(s) - depolarization , endoplasmic reticulum , biophysics , cyclopiazonic acid , chemistry , calcium , medicine , extracellular , endocrinology , serca , biochemistry , biology , atpase , enzyme
1 We hypothesized that enhanced voltage‐gated Ca 2+ channel current (VGCC) density in coronary smooth muscle cells of exercise‐trained miniature Yucatan pigs is compensated by other cellular Ca 2+ regulatory mechanisms to limit net myoplasmic free Ca 2+ accumulation. 2 Whole‐cell voltage clamp experiments demonstrated enhanced VGCC density in smooth muscle cells freshly dispersed from coronary arteries of exercise‐trained vs. sedentary animals. 3 In separate experiments using fura‐2 microfluorometry, we measured depolarization‐induced (80 m m KCl) accumulation of myoplasmic free Ba 2+ and free Ca 2+ . Both maximal rate and net accumulation of free Ba 2+ in response to membrane depolarization were increased in smooth muscle cells isolated from exercise‐trained pigs, consistent with an increased VGCC density. Depolarization also produced an enhanced maximal rate of free Ca 2+ accumulation in cells of exercise‐trained pigs; however, net accumulation of free Ca 2+ was not significantly increased suggesting enhanced Ca 2+ influx was compensated to limit net free Ca 2+ accumulation. 4 Inhibition of sarco‐endoplasmic reticulum Ca 2+ ‐transporting ATPase (SERCA; 10 μ m cyclopiazonic acid) and/or sarcolemmal Na + ‐Ca 2+ exchange (low extracellular Na + ) suggested neither mechanism compensated the enhanced VGCC in cells of exercise‐trained animals. 5 Local Ca 2+ ‐dependent inactivation of VGCC, assessed by buffering myoplasmic Ca 2+ with EGTA in the pipette and using Ca 2+ and Ba 2+ as charge carriers, was not different between cells of sedentary and exercise‐trained animals. 6 Our findings indicate that increased VGCC density is compensated by other cellular Ca 2+ regulatory mechanisms to limit net myoplasmic free Ca 2+ accumulation in smooth muscle cells of exercise‐trained animals. Further, SERCA, Na + ‐Ca 2+ exchange and local Ca 2+ ‐dependent inactivation of VGCC do not appear to function as compensatory mechanisms. Additional potential compensatory mechanisms include Ca 2+ extrusion via plasma membrane Ca 2+ ‐ATPase, mitochondrial uptake, myoplasmic Ca 2+ ‐binding proteins and other sources of VGCC inactivation.