Increased Na(+)-K+ pump number and decreased pump activity in soleus muscles in SHR

Abstract

We have previously demonstrated electrophysiological and contractile abnormalities in soleus muscles of the spontaneously hypertensive rat (SHR). The age-related decrease in force and fatigue resistance observed in SHR muscles may be produced by alterations in sarcolemmal ion conductance and/or Na+ pump function. The experiments reported in the present paper were designed to assess the functional capacity of the Na+ pump in 6- to 8- and 24- to 28-wk-old SHR and Wistar-Kyoto (WKY) soleus muscles and to correlate pump activity with Na+ pump number and binding affinity ([3H]ouabain binding). Functional capacity was determined by measuring the change in resting membrane potential (RMP) of soleus muscle fibers in response to agents that stimulate (epinephrine and insulin) or inhibit (ouabain) the pump and by measuring maximum ouabain-suppressible 86Rb+ uptake in Na(+)-loaded muscles. Na+ pump number and affinity were quantified by determining the specific binding of [3H]ouabain in soleus muscle slices. SHR soleus muscles contain a greater number of Na+ pump sites (ouabain binding sites) than are present in age-matched WKY muscles but also experience a significant decrease in pump activity with age. SHR may upregulate pump number in response to the significantly higher intracellular Na+ concentration found in soleus muscles at all the ages examined. The apparent reduction in pump capacity with age may play a major role in the observed age-related decrease in SHR soleus force and fatigue resistance.