Ischemic-like conditions (a glucose-free, pH 6.6 Tyrode solution bubbled with 100% N2) enhance L-type Ca current (I_Ca,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 I_Ca,L. Therefore, our goal was to explain why I_Ca,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 I_Ca,L; 2) inhibition of protein kinase A with H-89, or calcium/calmodulin-dependent protein kinase II with KN-93, reduced I_Ca,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 I_Ca,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.