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

¹Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, West Virginia; ²Department of Health and Kinesiology, Texas A&M University, College Station, Texas; ³Department of Applied Physiology and Kinesiology, Center for Exercise Science, University of Florida, Gainesville, Florida; ⁴Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia; and ⁵Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida

Submitted 16 September 2008 ; accepted in final form 24 April 2009

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 K_V channel expression and negative feedback regulation of myogenic tone increases with advancing age in arterioles from both oxidative and glycolytic muscles.

delayed rectifier potassium channel; calcium-activated potassium channel; iberiotoxin; 4-aminopyridine; K_V1.5

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				Highlights From the Literature Physiology, October 1, 2009; 24(5): 276 - 280. [Full Text] [PDF]