Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Antoons, G; Volders, PG; Stankovicova, T; Bito, V; Stengl, M; Vos, MA; Sipido, KR.
Window Ca2+ current and its modulation by Ca2+ release in hypertrophied cardiac myocytes from dogs with chronic atrioventricular block.
J Physiol. 2007; 579(Pt 1):147-160
Doi: 10.1113/jphysiol.2006.124222
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- Führende Autor*innen der Med Uni Graz
- Antoons Gudrun
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- Abstract:
- Torsades de pointes (TdP) ventricular tachycardia typically occurs in the setting of early afterdepolarizations; it contributes to arrhythmias and sudden death in congenital and acquired heart disease. Window L-type Ca2+ current (ICaL) has a central role in the arrhythmogenesis and may be particularly important under beta-adrenergic stimulation. We studied the properties of ICaL in myocytes from the dog with chronic atrioventricular block (cAVB) that has cardiac hypertrophy and an increased susceptibility to TdP. Peak ICaL densities at baseline (K+ - and Na+ -free solutions, 10 mmol l(-1) [EGTA]pip) in cAVB were comparable to control, but inactivation was shifted to the right, resulting in a larger window current area in cAVB. Under beta-adrenergic stimulation, the window current area was increased and shifted to the left, but less so in cAVB (maximum at -27 mV, versus -32 mV in control). ICaL during a step to -35 mV showed a transient reduction immediately after the peak. Test steps to 0 mV, simultaneous recording of [Ca2+]i and manipulation of sarcoplasmic reticulum (SR) Ca2+ release showed that this resulted from inhibition and fast recovery of ICaL with SR Ca2+ release. The extent of this dynamic modulation was larger in cAVB than in control (23 +/- 2% of the initially available current, versus 13 +/- 3%; P<0.05). Early afterdepolarizations (EADs) in cAVB myocytes under beta-adrenergic stimulation typically occurred in the window current voltage range and after decline of [Ca2+]i. In conclusion, in cAVB, the larger window current, its rightward shift and enhanced dynamic modulation by SR Ca2+ release may contribute to an increased incidence of EADs in cAVB under beta-adrenergic stimulation.
- Find related publications in this database (using NLM MeSH Indexing)
- Adrenergic beta-Agonists - pharmacology
- Animals -
- Buffers -
- Calcium - metabolism
- Calcium Channels, L-Type - metabolism
- Cardiomegaly - metabolism Cardiomegaly - pathology
- Chronic Disease -
- Disease Models, Animal -
- Dogs -
- Female -
- Heart Block - metabolism Heart Block - pathology
- Isoproterenol - pharmacology
- Male -
- Membrane Potentials - drug effects Membrane Potentials - physiology
- Myocytes, Cardiac - drug effects Myocytes, Cardiac - metabolism Myocytes, Cardiac - pathology
- Sarcoplasmic Reticulum - metabolism
- Torsades de Pointes - metabolism Torsades de Pointes - pathology