Ca entry-independent effects of L-type Ca channel modulators on Ca sparks in ventricular myocytes
نویسندگان
چکیده
Copello JA, Zima AV, Diaz-Sylvester PL, Fill M, Blatter LA. Ca entry-independent effects of L-type Ca channel modulators on Ca sparks in ventricular myocytes. Am J Physiol Cell Physiol 292: C2129–C2140, 2007. First published February 21, 2007; doi:10.1152/ajpcell.00437.2006.—During the cardiac action potential, Ca entry through dyhidropyridine receptor L-type Ca channels (DHPRs) activates ryanodine receptors (RyRs) Ca -release channels, resulting in massive Ca mobilization from the sarcoplasmic reticulum (SR). This global Ca release arises from spatiotemporal summation of many localized elementary Ca -release events, Ca sparks. We tested whether DHPRs modulate Ca sparks in a Ca entry-independent manner. Negative modulation by DHPR of RyRs via physical interactions is accepted in resting skeletal muscle but remains controversial in the heart. Ca sparks were studied in cat cardiac myocytes permeabilized with saponin or internally perfused via a patch pipette. Bathing and pipette solutions contained low Ca (100 nM). Under these conditions, Ca sparks were detected with a stable frequency of 3–5 sparks s 1 100 m . The DHPR blockers nifedipine, nimodipine, FS-2, and calciseptine decreased spark frequency, whereas the DHPR agonists Bay-K8644 and FPL-64176 increased it. None of these agents altered the spatiotemporal characteristics of Ca sparks. The DHPR modulators were also without effect on SR Ca load (caffeine-induced Ca transients) or sarco(endo)plasmic reticulum Ca -ATPase (SERCA) activity (Ca loading rates of isolated SR microsomes) and did not change cardiac RyR channel gating (planar lipid bilayer experiments). In summary, DHPR modulators affected spark frequency in the absence of DHPR-mediated Ca entry. This action could not be attributed to a direct action of DHPR modulators on SERCA or RyRs. Our results suggest that the activity of RyR Ca -release units in ventricular myocytes is modulated by Ca entry-independent conformational changes in neighboring DHPRs.
منابع مشابه
Ca2+ entry-independent effects of L-type Ca2+ channel modulators on Ca2+ sparks in ventricular myocytes.
During the cardiac action potential, Ca(2+) entry through dyhidropyridine receptor L-type Ca(2+) channels (DHPRs) activates ryanodine receptors (RyRs) Ca(2+)-release channels, resulting in massive Ca(2+) mobilization from the sarcoplasmic reticulum (SR). This global Ca(2+) release arises from spatiotemporal summation of many localized elementary Ca(2+)-release events, Ca(2+) sparks. We tested w...
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