Aging and muscle fiber type alter K⁺ channel contributions to the myogenic response in skeletal muscle arterioles

Aging diminishes myogenic tone in arterioles from skeletal muscle. Recent evidence indicates that both large-conductance Ca²⁺-activated (BK_Ca) and voltage-dependent (K_V) K⁺ channels mediate negative feedback control of the myogenic response. Thus we tested the hypothesis that aging increases the contributions of K_V and BK _Ca channels to myogenic regulation of vascular tone. Because myogenic responsiveness differs between oxidative and glycolytic muscles, we predicted that K_V and BK_Ca channel contributions to myogenic responsiveness vary with fiber type. Myogenic responses of first-order arterioles from the gastrocnemius and soleus muscles of 4- and 24-mo-old Fischer 344 rats were evaluated in the presence and absence of 4-aminopyridine (5 mM) or iberiotoxin (30 nM), inhibitors of K_V and BK_Ca, respectively. 4-Aminopyridine enhanced myogenic tone with aging and normalized age-related differences in both muscle types. By contrast, iberiotoxin eliminated age-related differences in soleus arterioles and had no effect in gastrocnemius vessels. K_V1.5 is an integral component of K _V channels in vascular smooth muscle; therefore, we determined the relative protein expression of K_V1.5, as well as BK_Ca, in soleus and gastrocnemius arterioles. Immunoblot analysis revealed no differences in K_V1.5 protein with aging or between variant fiber types, whereas BK_Ca protein levels declined with age in arterioles from both muscle groups. Collectively, these results suggest that the contribution of BK _Ca to myogenic regulation of vascular tone changes with age in soleus muscle arterioles, whereas increased KV channel expression and negative feedback regulation of myogenic tone increases with advancing age in arterioles from both oxidative and glycolytic muscles.