Similarities between early and delayed afterdepolarizations induced by isoproterenol in canine ventricular myocytes.
OBJECTIVE
This study aims at clarifying the role of cellular Ca2+ overload and spontaneous sarcoplasmic reticulum (SR) Ca2+ release in the generation of early afterdepolarizations (EAD) by isoproterenol. The involvement of a Ca(2+)-activated membrane current in isoproterenol-induced EAD is investigated.


METHODS
Membrane potential and contraction (an indicator of SR Ca2+ release) were recorded in canine left ventricular myocytes at pacing cycle lengths (CL) of 300-4000 ms. Threshold concentration for EAD was 20-50 mmol/l isoproterenol. Ni2+ (2.0-5.0 mmol/l) was used at normal and high (5.4 mmol/l) [Ca2+]o to examine the role of Ca2+ current and/or Na(+)-Ca2+ exchange (1Na-Ca) in EAD.


RESULTS
In all cells delayed afterdepolarizations (DAD) appeared during isoproterenol. In most (approximately equal to 70%) cells EAD were also generated, which were fast-pacing dependent, occurring only at CL of 400-1000 ms. EAD were always initiated by a delay in repolarization. Early aftercontractions preceded the EAD upstrokes, often occurring without them. They coincided with the initial delays in repolarization. During treatment with isoproterenol, Ni2+ and high [Ca2+]o, EAD and DAD were suppressed despite the continued presence of early and delayed aftercontractions.


CONCLUSIONS
Our data indicate that beta-adrenergic EAD share a common ionic mechanism with DAD in terms of cellular Ca2+ overload and spontaneous SR Ca2+ release. beta-Adrenergic EAD consist of two phases: (1) a conditional phase coinciding with the onset of an early aftercontraction, often followed by (2) an EAD upstroke. A Ca2(+)-activated membrane current, probably I Na-Ca, is necessary at least for the initiation of these EAD.
Volders
P G
PG
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
Kulcśar
A
A
Vos
M A
MA
Sipido
K R
KR
Wellens
H J
HJ
Lazzara
R
R
Szabo
B
B
D000200:Action Potentials / Q000187:drug effects; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002412:Cations; D002478:Cells, Cultured; D004285:Dogs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D009532:Nickel / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D000889:Anti-Arrhythmia Agents; D002412:Cations; D011412:Propanolamines; D009532:Nickel; C074334:almokalant; D007545:Isoproterenol; D002118:Calcium