title: Activation of calcium release assessed by calcium release-induced inactivation of calcium current in rat cardiac myocytes.
abstract: In mammalian cardiac myocytes, calcium released into the dyadic space rapidly inactivates calcium current (ICa). We used this Ca2+ release-dependent inactivation (RDI) of ICa as a local probe of sarcoplasmic reticulum Ca2+ release activation. In whole cell patch-clamped rat ventricular myocytes, Ca2+ entry induced by short prepulses from -50 mV to positive voltages caused suppression of peak ICa during a test pulse. The negative correlation between peak ICa suppression and ICa inactivation during the test pulse indicated that RDI evoked by the prepulse affected only calcium channels in those dyads in which calcium release was activated. Ca2+ ions injected during the prepulse and during the subsequent tail current suppressed peak ICa in the test pulse to a different extent. Quantitative analysis indicated that equal Ca2+ charge was 3.5 times less effective in inducing release when entering during the prepulse than when entering during the tail. Tail Ca2+ charge injected by the first voltage-dependent calcium channel (DHPR) openings was three times less effective than that injected by DHPR reopenings. These findings suggest that calcium release activation can be profoundly influenced by the recent history of L-type Ca2+ channel activity due to potentiation of ryanodine receptors (RyRs) by previous calcium influx. This conclusion was confirmed at the level of single RyRs in planar lipid bilayers: using flash photolysis of the calcium cage NP-EGTA to generate two sequential calcium stimuli, we showed that RyR activation in response to the second stimulus was four times higher than that in response to the first stimulus.
authors.affiliation: Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlárska 5, 833 34 Bratislava, Slovakia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Zahradníková
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Kubalová
authors.forename: Jana
authors.initials: J
authors.lastname: Pavelková
authors.forename: Sándor
authors.initials: S
authors.lastname: Györke
authors.forename: Ivan
authors.initials: I
authors.lastname: Zahradník
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D004553:Electric Conductivity; D004558:Electric Stimulation; D008297:Male; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium