Impaired BKCa channel function in native vascular smooth muscle from humans with type 2 diabetes

Madeline Nieves-Cintrón, Arsalan U. Syed, Olivia R. Buonarati, Robert R. Rigor, Matthew A. Nystoriak, Debapriya Ghosh, Kent C. Sasse, Sean M. Ward, Luis F. Santana, Johannes W. Hell, Manuel F. Navedo

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Large-conductance Ca2+-activated potassium (BKCa) channels are key determinants of vascular smooth muscle excitability. Impaired BKCa channel function through remodeling of BKCa β1 expression and function contributes to vascular complications in animal models of diabetes. Yet, whether similar alterations occur in native vascular smooth muscle from humans with type 2 diabetes is unclear. In this study, we evaluated BKCa function in vascular smooth muscle from small resistance adipose arteries of non-diabetic and clinically diagnosed type 2 diabetic patients. We found that BKCa channel activity opposes pressure-induced constriction in human small resistance adipose arteries, and this is compromised in arteries from diabetic patients. Consistent with impairment of BKCa channel function, the amplitude and frequency of spontaneous BKCa currents, but not Ca2+ sparks were lower in cells from diabetic patients. BKCa channels in diabetic cells exhibited reduced Ca2+ sensitivity, single-channel open probability and tamoxifen sensitivity. These effects were associated with decreased functional coupling between BKCa α and β1 subunits, but no change in total protein abundance. Overall, results suggest impairment in BKCa channel function in vascular smooth muscle from diabetic patients through unique mechanisms, which may contribute to vascular complications in humans with type 2 diabetes.

Original languageEnglish (US)
Article number14058
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

Vascular Smooth Muscle
Type 2 Diabetes Mellitus
Arteries
Blood Vessels
Potassium Channels
Tamoxifen
Constriction
Animal Models
Pressure
Proteins

ASJC Scopus subject areas

  • General

Cite this

Impaired BKCa channel function in native vascular smooth muscle from humans with type 2 diabetes. / Nieves-Cintrón, Madeline; Syed, Arsalan U.; Buonarati, Olivia R.; Rigor, Robert R.; Nystoriak, Matthew A.; Ghosh, Debapriya; Sasse, Kent C.; Ward, Sean M.; Santana, Luis F.; Hell, Johannes W.; Navedo, Manuel F.

In: Scientific Reports, Vol. 7, No. 1, 14058, 01.12.2017.

Research output: Contribution to journalArticle

Nieves-Cintrón, Madeline ; Syed, Arsalan U. ; Buonarati, Olivia R. ; Rigor, Robert R. ; Nystoriak, Matthew A. ; Ghosh, Debapriya ; Sasse, Kent C. ; Ward, Sean M. ; Santana, Luis F. ; Hell, Johannes W. ; Navedo, Manuel F. / Impaired BKCa channel function in native vascular smooth muscle from humans with type 2 diabetes. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
@article{b97c6ce259c94e2ab4e1ab58e516896b,
title = "Impaired BKCa channel function in native vascular smooth muscle from humans with type 2 diabetes",
abstract = "Large-conductance Ca2+-activated potassium (BKCa) channels are key determinants of vascular smooth muscle excitability. Impaired BKCa channel function through remodeling of BKCa β1 expression and function contributes to vascular complications in animal models of diabetes. Yet, whether similar alterations occur in native vascular smooth muscle from humans with type 2 diabetes is unclear. In this study, we evaluated BKCa function in vascular smooth muscle from small resistance adipose arteries of non-diabetic and clinically diagnosed type 2 diabetic patients. We found that BKCa channel activity opposes pressure-induced constriction in human small resistance adipose arteries, and this is compromised in arteries from diabetic patients. Consistent with impairment of BKCa channel function, the amplitude and frequency of spontaneous BKCa currents, but not Ca2+ sparks were lower in cells from diabetic patients. BKCa channels in diabetic cells exhibited reduced Ca2+ sensitivity, single-channel open probability and tamoxifen sensitivity. These effects were associated with decreased functional coupling between BKCa α and β1 subunits, but no change in total protein abundance. Overall, results suggest impairment in BKCa channel function in vascular smooth muscle from diabetic patients through unique mechanisms, which may contribute to vascular complications in humans with type 2 diabetes.",
author = "Madeline Nieves-Cintr{\'o}n and Syed, {Arsalan U.} and Buonarati, {Olivia R.} and Rigor, {Robert R.} and Nystoriak, {Matthew A.} and Debapriya Ghosh and Sasse, {Kent C.} and Ward, {Sean M.} and Santana, {Luis F.} and Hell, {Johannes W.} and Navedo, {Manuel F.}",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41598-017-14565-9",
language = "English (US)",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Impaired BKCa channel function in native vascular smooth muscle from humans with type 2 diabetes

AU - Nieves-Cintrón, Madeline

AU - Syed, Arsalan U.

AU - Buonarati, Olivia R.

AU - Rigor, Robert R.

AU - Nystoriak, Matthew A.

AU - Ghosh, Debapriya

AU - Sasse, Kent C.

AU - Ward, Sean M.

AU - Santana, Luis F.

AU - Hell, Johannes W.

AU - Navedo, Manuel F.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Large-conductance Ca2+-activated potassium (BKCa) channels are key determinants of vascular smooth muscle excitability. Impaired BKCa channel function through remodeling of BKCa β1 expression and function contributes to vascular complications in animal models of diabetes. Yet, whether similar alterations occur in native vascular smooth muscle from humans with type 2 diabetes is unclear. In this study, we evaluated BKCa function in vascular smooth muscle from small resistance adipose arteries of non-diabetic and clinically diagnosed type 2 diabetic patients. We found that BKCa channel activity opposes pressure-induced constriction in human small resistance adipose arteries, and this is compromised in arteries from diabetic patients. Consistent with impairment of BKCa channel function, the amplitude and frequency of spontaneous BKCa currents, but not Ca2+ sparks were lower in cells from diabetic patients. BKCa channels in diabetic cells exhibited reduced Ca2+ sensitivity, single-channel open probability and tamoxifen sensitivity. These effects were associated with decreased functional coupling between BKCa α and β1 subunits, but no change in total protein abundance. Overall, results suggest impairment in BKCa channel function in vascular smooth muscle from diabetic patients through unique mechanisms, which may contribute to vascular complications in humans with type 2 diabetes.

AB - Large-conductance Ca2+-activated potassium (BKCa) channels are key determinants of vascular smooth muscle excitability. Impaired BKCa channel function through remodeling of BKCa β1 expression and function contributes to vascular complications in animal models of diabetes. Yet, whether similar alterations occur in native vascular smooth muscle from humans with type 2 diabetes is unclear. In this study, we evaluated BKCa function in vascular smooth muscle from small resistance adipose arteries of non-diabetic and clinically diagnosed type 2 diabetic patients. We found that BKCa channel activity opposes pressure-induced constriction in human small resistance adipose arteries, and this is compromised in arteries from diabetic patients. Consistent with impairment of BKCa channel function, the amplitude and frequency of spontaneous BKCa currents, but not Ca2+ sparks were lower in cells from diabetic patients. BKCa channels in diabetic cells exhibited reduced Ca2+ sensitivity, single-channel open probability and tamoxifen sensitivity. These effects were associated with decreased functional coupling between BKCa α and β1 subunits, but no change in total protein abundance. Overall, results suggest impairment in BKCa channel function in vascular smooth muscle from diabetic patients through unique mechanisms, which may contribute to vascular complications in humans with type 2 diabetes.

UR - http://www.scopus.com/inward/record.url?scp=85032290821&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85032290821&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-14565-9

DO - 10.1038/s41598-017-14565-9

M3 - Article

C2 - 29070899

AN - SCOPUS:85032290821

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 14058

ER -