Key result
1.0 µmol/L K201 significantly reduced the amplitude of diastolic contractile events from 4.90% to 0.77% resting cell length in rat cardiomyocytes during β-adrenergic stimulation.
Why the study?
Does K201 reduce spontaneous diastolic Ca2+ release and associated contractions during β-adrenergic stimulation in isolated rat ventricular cardiomyocytes?
Does K201 reduce spontaneous diastolic Ca2+ release and associated contractions during β-adrenergic stimulation in isolated rat ventricular cardiomyocytes?
K201 reduces spontaneous diastolic Ca2+ release and associated contractions in isolated rat cardiomyocytes, providing a cellular mechanism for its potential to limit contractile dysfunction in vivo.
Answers are grounded in this paper and cite their sources.
May attenuate stress-induced diastolic dysfunction; leaves open translation to in vivo HF or arrhythmia models.
K201 has previously been shown to reduce diastolic contractions in vivo during β-adrenergic stimulation and elevated extracellular calcium concentration ([Ca(2+)](o)). The present study characterised the effect of K201 on electrically stimulated and spontaneous diastolic sarcoplasmic reticulum (SR)-mediated Ca(2+) release and contractile events in isolated rat cardiomyocytes during β-adrenergic stimulation and elevated [Ca(2+)](o). Parallel experiments using confocal microscopy examined spontaneous diastolic Ca(2+) release events at an enhanced spatiotemporal resolution. 1.0 μmol/L K201 in the presence of 150 nmol/L isoproterenol (ISO) and 4.75 mmol/L [Ca(2+)](o) significantly decreased the amplitude of diastolic contractions to ~16% of control levels. The stimulated free Ca(2+) transient amplitude was significantly reduced, but stimulated cell shortening was not significantly altered. When intracellular buffering was taken into account, K201 led to an increase in action potential-induced SR Ca(2+) release. Myofilament sensitivity to Ca(2+) was not changed by K201. Confocal microscopy revealed diastolic events composed of multiple Ca(2+) waves (2-3) originating at various points along the cardiomyocyte length during each diastolic period. 1.0 μmol/L K201 significantly reduced the (a) frequency of diastolic events and (b) initiation points/diastolic interval in the remaining diastolic events to 61% and 71% of control levels respectively. 1.0 μmol/L K201 can reduce the probability of spontaneous diastolic Ca(2+) release and their associated contractions which may limit the propensity for the contractile dysfunction observed in vivo.
No takes yet. Share an insight, caveat, or question.
Elliott et al. (2011) studied Normal (isolated ventricular cardiomyocytes) (n=23). K201 (JTV-519) vs. Vehicle (DMSO) / Control conditions (isoproterenol + elevated Ca2+) was evaluated on Amplitude of diastolic contractile events (% resting cell length) (p=<0.05). 1.0 µmol/L K201 significantly reduced the amplitude of diastolic contractile events from 4.90% to 0.77% resting cell length in rat cardiomyocytes during β-adrenergic stimulation.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: