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Am J Physiol Heart Circ Physiol 293: H2986-H2994, 2007. First published August 31, 2007; doi:10.1152/ajpheart.00491.2007
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Simulated ischemia enhances L-type calcium current in pacemaker cells isolated from the rabbit sinoatrial node

Yi-Mei Du1,2 and Richard D. Nathan1

1Department of Cell Physiology and Molecular Biophysics, Texas Tech University Health Sciences Center, Lubbock, Texas; and 2Department of Cardiology, Institute of Cardiovascular Diseases, Ion Channelopathy Research Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Submitted 24 April 2007 ; accepted in final form 29 August 2007

Ischemic-like conditions (a glucose-free, pH 6.6 Tyrode solution bubbled with 100% N2) enhance L-type Ca current (ICa,L) in single pacemaker cells (PCs) isolated from the rabbit sinoatrial node (SAN). In contrast, studies of ventricular myocytes have shown that acidic extracellular pH, as employed in our "ischemic" Tyrode, reduces ICa,L. Therefore, our goal was to explain why ICa,L is increased by "ischemia" in SAN PCs. The major findings were the following: 1) blockade of Ca-induced Ca release with ryanodine, exposure of PCs to BAPTA-AM, or replacement of extracellular Ca2+ with Ba2+ failed to prevent the ischemia-induced enhancement of ICa,L; 2) inhibition of protein kinase A with H-89, or calcium/calmodulin-dependent protein kinase II with KN-93, reduced ICa,L but did not prevent its augmentation by ischemia; 3) ischemic Tyrode or pH 6.6 Tyrode shifted the steady-state inactivation curve in the positive direction, thereby reducing inactivation; 4) ischemic Tyrode increased the maximum conductance but did not affect the activation curve; 5) in rabbit atrial myocytes isolated and studied with exactly the same techniques used for SAN PCs, ischemic Tyrode reduced the maximum conductance and shifted the activation curve in the positive direction; pH 6.6 Tyrode also shifted the steady-state inactivation curve in the positive direction. We conclude that the acidic pH of ischemic Tyrode enhances ICa,L in SAN PCs, because it increases the maximum conductance and reduces inactivation. Furthermore, the opposite results obtained with rabbit atrial myocytes cannot be explained by differences in cell isolation or patch-clamp techniques.

acidosis; protein kinase A; calcium/calmodulin-dependent protein kinase II; calcium-induced inactivation; rabbit atrial myocytes


Address for reprint requests and other correspondence: Y-M Du, Dept. of Cell Physiology and Molecular Biophysics, Texas Tech Univ. Health Sciences Ctr., 3601 4th St., Lubbock, TX 79430 (e-mail: yimeidu{at}hotmail.com)






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