Role of calcium loading in early afterdepolarizations generated by Cs+ in canine and guinea pig Purkinje fibers.
BACKGROUND
Our previous observations indicate that the Na+:Ca2+ exchange current (INa:Ca) plays an important role in early afterdepolarizations occurring at more negative Vm (L-EAD). The purpose of these studies was to examine the role of Ca(2+)-loading, which stimulates INa:Ca, in generation of L-EAD.


RESULTS
Purkinje strands and preparations of ventricular myocardium from dogs and guinea pigs were superfused with oxygenated physiologic buffer solutions at 37 degrees C. To induce EADs, [K+]o was reduced to 2.0 to 3.0 mM and [Cs+]o (3.6 to 4.0 mM) was added at slow rates of < or = 0.3 Hz. Isometric contraction in canine Purkinje strands and guinea pig papillary muscles doubled in 1-hour exposure to Cs+ and low [K+]o at slow rates and the uptake of 45Ca2+ was approximately doubled after 30 minutes. Forty-three percent of Purkinje fibers developed L-EAD after a latent period of 17 to 123 minutes of exposure. Ouabain (0.2 microM) suppressed L-EAD within 10 minutes reversibly. Ca(2+)-loading (low [Na+]o or high [Ca2+]o) for 5 to 10 minutes before exposure to Cs+, low [K+]o, and slow rates resulted in rapid development of L-EAD in all preparations during subsequent exposure. In Ca(2+)-loaded preparations, delayed afterdepolarizations (DADs) as well as L-EADs developed.


CONCLUSIONS
Reduction of K+ currents with Cs+, low [K+]o, and slow rates induced L-EAD in a fraction of Purkinje fibers after a latent period during which Ca(2+)-loading of the sarcoplasmic reticulum occurred, while fibers preloaded with Ca2+ developed L-EAD rapidly and uniformly. These findings indicate that Ca(2+)-loading is a critical condition for the development of L-EAD. Early suppression of L-EAD by ouabian suggests a dependence of L-EAD on low [Na+]i. These findings implicate INa:Ca in the generation of L-EAD.
Szabo
B
B
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
Kovacs
T
T
Lazzara
R
R
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002586:Cesium / Q000494:pharmacology*; D004285:Dogs; D004594:Electrophysiology; D006168:Guinea Pigs; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology*; D011930:Reaction Time
D002586:Cesium; D010042:Ouabain; D011188:Potassium; D002118:Calcium