Impaired BKCa channel function in native vascular smooth muscle from diabetic patients

Abstract

Increased vascular tone and impaired vascular function are major complications during diabetes. Large‐conductance Ca2+‐activated potassium (BKCa) channels are important regulators of vascular smooth muscle cell contractility and arterial tone. Whereas multiple reports indicate that BKCa channel function is impaired in murine models of diabetes and in immortalized cell lines from diabetic human subjects, whether a similar alteration occurs in native vascular smooth muscle cells from diabetic patients has not been clearly established. Here, we examine and compared BKCa channel function in native vascular smooth muscle cells from obese non‐diabetic and diabetic patients undergoing bariatric surgery using patch‐clamp electrophysiology and confocal microscopy. We found that the amplitude and frequency of spontaneous transient outward currents (STOCs), which are produced by the activation of BKCa channels coupled to Ca2+ sparks, are significantly decreased in human diabetic cells. Ca2+ sparks amplitude and frequency was not different between human non‐diabetic and diabetic cells, indicating that impairment in STOC activity occurs at the BKCa channel level. Consistent with this, BKCa channels in human diabetic cells showed an apparent reduction in Ca2+ sensitivity as compared to non‐diabetic cells. These results suggest impaired BKCa channel function due to aberrant Ca2+ sensitivity in native vascular smooth muscle cells from diabetic patients, which may contribute to the development of vascular complications in humans with diabetes.Support or Funding InformationThis work was supported by grants NIH‐HL098200 and NIH‐HL121059, and AHA‐14GRNT18730054 to MFN.