Calcitonin gene-related peptide stimulates active Na(+)-K+ transport in rat soleus muscle.

Calcitonin gene-related peptide (CGRP) is found in a wide variety of tissues, including sensory and motor nerve endings in skeletal muscle. After intense electrical stimulation or K(+)-induced depolarization, CGRP can be released from nerve terminals and bound to receptors on sarcolemma. We show here that CGRP (rat and human) and salmon calcitonin stimulate 22Na extrusion and the influx of 86Rb and 42K in isolated rat soleus muscle. This leads to a pronounced (up to 56%) decrease in intracellular Na+, a minor increase in intracellular K+, and hyperpolarization. All these effects were blocked by ouabain or cooling, indicating that they reflect an acute stimulation of active electrogenic Na(+)-K+ transport. Capsaicin, which induces release of CGRP from sensory nerve endings, was found to exert similar effects on Na(+)-K+ transport. Various Na(+)-K+ pump-stimulating agents have been shown to counteract the inhibitory effect of a high extracellular concentration of K+ ([K+]o) on muscle contractility (4, 20). CGRP and capsaicin were likewise found to improve contractile performance of muscles inhibited by high [K+]o, and these effects were blocked by ouabain. CGRP might play a role in the maintenance of Na(+)-K+ gradients and excitability during intensive muscle work, known to be associated with an acute rise in the interstitial K+ concentration.