Kv7 channels in mesenteric arteries of male UC Davis type 2 diabetes mellitus (UCD-T2DM) rats: Responses to activation and inhibition
Poster Number
44
Faculty Mentor Name
Roshanak Rahimian
Research or Creativity Area
Pharmacy
Abstract
Voltage-gated potassium (Kv) channels are critical for regulating vascular contractility in both rodent and human blood vessels. During smooth muscle depolarization, Kv7 channels are essential in regulating vascular tone by potassium ion efflux through the plasma membrane. However, their roles in pathological conditions like diabetes are not well understood. It has been shown that muscarinic and adrenergic arterial responses are altered in diabetes. In this study, we examine the role of Kv7 channels in mesenteric arteries in the context of diabetes.
Purpose
We hypothesize that both the function and pharmacology of Kv7 channels are altered in mesenteric arteries from diabetic rats.
To address this hypothesis, third-order mesenteric arteries were collected from three groups of male rats: 1) Sprague Dawley (SD), 2) UC Davis type 2 diabetes mellitus (UCD-T2DM) prediabetic rats, and 3) UCD-T2DM rats that had been diabetic for 3 months. Body weight, blood glucose, HbA1c, adipose-to-body weight ratio, and glucose tolerance test (GTT) were measured in the experimental groups. Endothelium-dependent and -independent vasorelaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) in phenylephrine (PE)-precontracted mesenteric arteries were assessed using wire myography. Furthermore, vasorelaxation responses to retigabine (Kv7 channel activator) and vasoconstriction responses to PE in the presence and absence of XE991 (Kv7 channel blocker) were measured.
Results
The diabetic group exhibited decreased body weight and adipose-to-body weight ratio, alongside elevated fasting blood glucose and HbA1c levels compared to other experimental groups. Furthermore, GTT was markedly impaired in both prediabetic and diabetic states. ACh-induced vasorelaxation was significantly impaired in both the prediabetic and diabetic groups compared to controls, with a more pronounced effect in the diabetic group. Diabetic rats also showed a significantly reduced sensitivity to SNP and retigabine-induced vasorelaxation compared to the other two groups. Pretreatment with XE991 enhanced PE-induced vasoconstriction in all three groups, with the strongest potentiation observed in the diabetic group.
Significance
In conclusion, our data shows that impaired responses to ACh and SNP, as well as altered responses to Kv7 channel activation or inhibition in the mesenteric arteries of UCD-T2DM rats, are dependent on the diabetic state. We have previously reported the mechanisms for the impairment of ACh and SNP responses in the arteries of UCD-T2DM rats. Further studies are needed to elucidate the mechanisms underlying the altered vascular responses involving Kv7 channels and their association with changes in vascular tone in this model.
Location
University of the Pacific, DeRosa University Center
Start Date
26-4-2025 10:00 AM
End Date
26-4-2025 1:00 PM
Kv7 channels in mesenteric arteries of male UC Davis type 2 diabetes mellitus (UCD-T2DM) rats: Responses to activation and inhibition
University of the Pacific, DeRosa University Center
Voltage-gated potassium (Kv) channels are critical for regulating vascular contractility in both rodent and human blood vessels. During smooth muscle depolarization, Kv7 channels are essential in regulating vascular tone by potassium ion efflux through the plasma membrane. However, their roles in pathological conditions like diabetes are not well understood. It has been shown that muscarinic and adrenergic arterial responses are altered in diabetes. In this study, we examine the role of Kv7 channels in mesenteric arteries in the context of diabetes.
