Age-Dependent Regulation of Kv7.4/7.5 Channels and Aortic Contractility in young and adult Male Rats
Faculty Mentor Name
Roshanak Rahimian
Research or Creativity Area
Engineering & Computer Science
Abstract
Age-related vascular stiffening is a key contributor to cardiovascular disease; however, its underlying molecular mechanisms remain incompletely understood. Voltage-gated potassium channels of the Kv7 family help stabilize membrane potential and promote vasorelaxation, but their specific role in large elastic arteries is not well characterized. This study examined how age influences the expression and function of Kv7.4 and Kv7.5 in the thoracic aorta of young and adult male Sprague-Dawley rats. Aortic rings from young (1-month) and adult (7-month) rats were analyzed using wire myography to measure phenylephrine-induced contraction and retigabine-mediated relaxation, followed by quantitative PCR to assess Kv7 subunit expression. These approaches allowed for both functional and molecular evaluation of vascular changes associated with age. Adult rats demonstrated augmented vasoconstrictive responses along with enhanced relaxation to Kv7 channel activation. This pattern suggests that while vascular tone increases
with age, there may also be adaptive mechanisms that help counterbalance this effect. qPCR analysis revealed a significant upregulation of Kv7.4 and Kv7.5 transcripts with age. The increased expression of these subunits is consistent with the observed functional responses and supports the idea that Kv7 channels play an active role in regulating vascular tone in aging vessels. These findings suggest that increased Kv7 channel expression may represent a compensatory adaptation to age-associated elevations in vascular tone. Targeting Kv7 channels may offer a promising therapeutic approach to preserve aortic function and mitigate age-related vascular dysfunction, particularly in conditions associated with increased arterial stiffness and impaired vasodilation.
Age-Dependent Regulation of Kv7.4/7.5 Channels and Aortic Contractility in young and adult Male Rats
Age-related vascular stiffening is a key contributor to cardiovascular disease; however, its underlying molecular mechanisms remain incompletely understood. Voltage-gated potassium channels of the Kv7 family help stabilize membrane potential and promote vasorelaxation, but their specific role in large elastic arteries is not well characterized. This study examined how age influences the expression and function of Kv7.4 and Kv7.5 in the thoracic aorta of young and adult male Sprague-Dawley rats. Aortic rings from young (1-month) and adult (7-month) rats were analyzed using wire myography to measure phenylephrine-induced contraction and retigabine-mediated relaxation, followed by quantitative PCR to assess Kv7 subunit expression. These approaches allowed for both functional and molecular evaluation of vascular changes associated with age. Adult rats demonstrated augmented vasoconstrictive responses along with enhanced relaxation to Kv7 channel activation. This pattern suggests that while vascular tone increases
with age, there may also be adaptive mechanisms that help counterbalance this effect. qPCR analysis revealed a significant upregulation of Kv7.4 and Kv7.5 transcripts with age. The increased expression of these subunits is consistent with the observed functional responses and supports the idea that Kv7 channels play an active role in regulating vascular tone in aging vessels. These findings suggest that increased Kv7 channel expression may represent a compensatory adaptation to age-associated elevations in vascular tone. Targeting Kv7 channels may offer a promising therapeutic approach to preserve aortic function and mitigate age-related vascular dysfunction, particularly in conditions associated with increased arterial stiffness and impaired vasodilation.
