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Acta Physiologica 2011; Volume 202, Supplement 685
Scandinavian Physiological Society's Annual Meeting
8/12/2011-8/14/2011
Bergen, Norway
RYANODINE RECEPTOR SENSITIVITY DETERMINES CA2+ WAVE VELOCITY IN CARDIOMYOCYTES
Abstract number: 8.1.2
LOOSE1 KO, SADREDINI1 MN, SEJERSTED1 OM, STOKKE1 MK, LOUCH1 WE
1Institute for Experimental Medical Research, Oslo University Hospital, Ullevl, N-0407 Oslo, Norway; Email: [email protected]
Aims:
In cardiomyocytes, arrhythmias can be caused by spontaneous release of Ca2+ from the sarcoplasmic reticulum (SR) via the SR Ca2+ release channel (RyR). Such release may initiate a self-propagating process called Ca2+ waves, which may trigger spontaneous action potentials. Importantly, this process may be augmented when waves propagate more rapidly. We have investigated the role of RyR sensitivity and SR Ca2+ content in regulating Ca2+ wave propagation.
Methods:
Ca2+ waves were studied in isolated ventricular cardiomyocytes from mice using confocal microscopy and Ca2+ fluorescent dyes.
Results:
To investigate the effect of increased RyR Ca2+ sensitivity, we rapidly exposed cells to 1 mM caffeine. The first wave following caffeine exposure exhibited increased propagation velocity (p< 0.05). However, at steady-state, velocity was not altered from pre-treatment values, although mean wave magnitude and SR Ca2+ content were reduced (p< 0.05). The opposite intervention, i.e. partial RyR blockade with 100 mM tetracaine increased wave magnitude and SR Ca2+ content at steady state (p< 0.05) but did not alter wave speed. These observations suggest that SR content-induced alterations in RyR sensitivity could account from differences in wave speed between initial and steady-state conditions. To test this hypothesis, the effect of decreasing SR Ca2+ over time was examined using 5 Hz stimulation followed by a pause. Wave speed was observed to progressively decline following the termination of stimulation (p< 0.05).
Conclusion:
Our data suggest that RyR sensitivity is an important determinant of Ca2+ wave speed. An induced increase in RyR sensitivity, such as that reported in heart failure, increases wave speed only until steady-state reduction in SR content counteracts such effects.
To cite this abstract, please use the following information:
Acta Physiologica 2011; Volume 202, Supplement 685 :8.1.2