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

Abstract

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. 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, (14)C-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. 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 (14)C-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. 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.