Role of Na+,K+ pumps in restoring contractility following loss of cell membrane integrity in rat skeletal muscle

Background and aim: In skeletal muscles, electrical shocks may elicit acute loss of force, possibly related to increased plasma membrane permeability, induced by electroporation (EP). We explore the role of the Na+,K+ pumps in force recovery after EP. Methods Isolated rat soleus or extensor digitorum longus (EDL) muscles were exposed to EP paradigms in the range 100-800 V cm(-1), and changes in tetanic force, Na+,K+ contents, membrane potential, C-14-sucrose space and the release of the intracellular enzyme lactic acid dehydrogenase (LDH) were characterized. The effects of Na+,K+ pump stimulation or inhibition were followed. Results: Electroporation caused voltage-dependent loss of force, followed by varying rates and degrees of recovery. EP induced a reversible loss of K+ and gain of Na+, which was not suppressed by tetrodotoxin, but associated with increased C-14-sucrose space and release of LDH. In soleus, EP at 500 V cm(-1) induced complete loss of force, followed by a spontaneous, partial recovery. Stimulation of active Na+,K+ transport by adrenaline, the beta(2)-agonist salbutamol, calcitonin gene-related peptide (CGRP) and dibutyryl cyclic AMP increased initial rate of force recovery by 183-433% and steady-state force level by 104-143%. These effects were blocked by ouabain (10(-3) m), which also completely suppressed spontaneous force recovery. EP caused rapid and marked depolarization, followed by a repolarization, which was accelerated by salbutamol. Also in EDL, EP caused complete loss of force, followed by a spontaneous partial recovery, which was markedly stimulated by salbutamol. Conclusion: Electroporation induces reversible depolarization, partial rundown of Na+,K+ gradients, cell membrane leakage and loss of force. This may explain the paralysis elicited by electrical shocks. Na+,K+ pump stimulation promotes restoration of contractility, possibly via its electrogenic action. The major new information is that the Na+,K+ pumps are sufficient to compensate a simple mechanical leakage. This may be important for force recovery in leaky muscle fibres.