Effect of purinergic receptor activation on Na+-K+ pump activity, excitability, and function in depolarized skeletal muscle

Broch-Lips M, Pedersen TH, Nielsen OB. Effect of purinergic receptor activation on Na+-K+ pump activity, excitability, and function in depolarized skeletal muscle. Am J Physiol Cell Physiol 298: C1438-C1444, 2010. First published March 3, 2010; doi:10.1152/ajpcell.00361.2009.-Activity- induced elevation of extracellular purines and pyrimidines has been associated with autocrine and paracrine signaling in many tissues. Here we investigate the effect of purinergic signaling for the excitability and contractility of depolarized skeletal muscle. Muscle excitability was experimentally depressed by elevating the extracellular K+ from 4 to 10 mM, which reduced the tetanic force to 24 +/- 2% of the force at 4 mM K+. Upon addition of 1 mM ATP, however, the force recovered to 65 +/- 8% of the control force (P < 0.001, n = 5). A similar recovery was seen with ADP, but not with UTP or adenosine. The ATP-induced force recovery could be inhibited by P2Y(1) receptor antagonists (3 mu M SCH-202676 or 1 mu M MRS-2500). A fourfold increase in M-wave area demonstrated that the ATP-induced force recovery was associated with restoration of muscle excitability (P < 0.05, n = 4). Experiments using Rb-86(+) as a tracer for K+ showed that ATP also induced a twofold increase in the activity of muscle Na+-K+ pumps. The force recovery and the stimulation of the Na+-K+ pump activity by ATP were inhibited by 50 mu M of the phospholipase C inhibitor U-73122. It is concluded that purinergic signaling can increase the Na+-K+ pump activity and improve force and excitability of depolarized skeletal muscles. This novel purinergic regulation may be important for the maintenance of muscle excitability during intense exercise, where the extracellular K+ can increase substantially.