β-Adrenergic stimulation increases the intra-sarcoplasmic reticulum Ca2+ threshold for Ca2+ wave generation. Domeier, T., Maxwell, J., & Blatter, L. J Physiol, 590(23):6093–6108, December, 2012.
β-Adrenergic stimulation increases the intra-sarcoplasmic reticulum Ca2+ threshold for Ca2+ wave generation. [link]Paper  doi  abstract   bibtex   
β-Adrenergic signalling induces positive inotropic effects on the heart that associate with pro-arrhythmic spontaneous Ca(2+) waves. A threshold level of sarcoplasmic reticulum (SR) Ca(2+) ([Ca(2+)](SR)) is necessary to trigger Ca(2+) waves, and whether the increased incidence of Ca(2+) waves during β-adrenergic stimulation is due to an alteration in this threshold remains controversial. Using the low-affinity Ca(2+) indicator fluo-5N entrapped within the SR of rabbit ventricular myocytes, we addressed this controversy by directly monitoring [Ca(2+)](SR) and Ca(2+) waves during β-adrenergic stimulation. Electrical pacing in elevated extracellular Ca(2+) ([Ca(2+)](o) = 7 mM) was used to increase [Ca(2+)](SR) to the threshold where Ca(2+) waves were consistently observed. The β-adrenergic agonist isoproterenol (ISO; 1 μM) increased [Ca(2+)](SR) well above the control threshold and consistently triggered Ca(2+) waves. However, when [Ca(2+)](SR) was subsequently lowered in the presence of ISO (by lowering [Ca(2+)](o) to 1 mM and partially inhibiting sarcoplasmic/endoplasmic reticulum calcium ATPase with cyclopiazonic acid or thapsigargin), Ca(2+) waves ceased to occur at a [Ca(2+)](SR) that was higher than the control threshold. Furthermore, for a set [Ca(2+)](SR) level the refractoriness of wave occurrence (Ca(2+) wave latency) was prolonged during β-adrenergic stimulation, and was highly dependent on the extent that [Ca](SR) exceeded the wave threshold. These data show that acute β-adrenergic stimulation increases the [Ca(2+)](SR) threshold for Ca(2+) waves, and therefore the primary cause of Ca(2+) waves is the robust increase in [Ca(2+)](SR) above this higher threshold level. Elevation of the [Ca(2+)](SR) wave threshold and prolongation of wave latency represent potentially protective mechanisms against pro-arrhythmogenic Ca(2+) release during β-adrenergic stimulation.
@article{domeier_-adrenergic_2012,
	title = {β-{Adrenergic} stimulation increases the intra-sarcoplasmic reticulum {Ca}2+ threshold for {Ca}2+ wave generation.},
	volume = {590},
	url = {https://www.ncbi.nlm.nih.gov/pubmed/22988136},
	doi = {10.1113/jphysiol.2012.236117},
	abstract = {β-Adrenergic signalling induces positive inotropic effects on the heart that associate with pro-arrhythmic spontaneous Ca(2+) waves. A threshold level of sarcoplasmic reticulum (SR) Ca(2+) ([Ca(2+)](SR)) is necessary to trigger Ca(2+) waves, and whether the increased incidence of Ca(2+) waves during β-adrenergic stimulation is due to an alteration in this threshold remains controversial. Using the low-affinity Ca(2+) indicator fluo-5N entrapped within the SR of rabbit ventricular myocytes, we addressed this controversy by directly monitoring [Ca(2+)](SR) and Ca(2+) waves during β-adrenergic stimulation. Electrical pacing in elevated extracellular Ca(2+) ([Ca(2+)](o) = 7 mM) was used to increase [Ca(2+)](SR) to the threshold where Ca(2+) waves were consistently observed. The β-adrenergic agonist isoproterenol (ISO; 1 μM) increased [Ca(2+)](SR) well above the control threshold and consistently triggered Ca(2+) waves. However, when [Ca(2+)](SR) was subsequently lowered in the presence of ISO (by lowering [Ca(2+)](o) to 1 mM and partially inhibiting sarcoplasmic/endoplasmic reticulum calcium ATPase with cyclopiazonic acid or thapsigargin), Ca(2+) waves ceased to occur at a [Ca(2+)](SR) that was higher than the control threshold. Furthermore, for a set [Ca(2+)](SR) level the refractoriness of wave occurrence (Ca(2+) wave latency) was prolonged during β-adrenergic stimulation, and was highly dependent on the extent that [Ca](SR) exceeded the wave threshold. These data show that acute β-adrenergic stimulation increases the [Ca(2+)](SR) threshold for Ca(2+) waves, and therefore the primary cause of Ca(2+) waves is the robust increase in [Ca(2+)](SR) above this higher threshold level. Elevation of the [Ca(2+)](SR) wave threshold and prolongation of wave latency represent potentially protective mechanisms against pro-arrhythmogenic Ca(2+) release during β-adrenergic stimulation.},
	language = {eng},
	number = {23},
	journal = {J Physiol},
	author = {Domeier, TL and Maxwell, JT and Blatter, LA},
	month = dec,
	year = {2012},
	keywords = {Sarcoplasmic Reticulum Calcium-Transporting ATPases},
	pages = {6093--6108}
}

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