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Impaired BK Ca channel function in native vascular smooth muscle from diabetic patients
Author(s) -
NievesCintron Madeline,
Buonarati Olivia R,
Rigor Robert,
Sasse Kent C,
Ward Sean M,
Hell Johannes W,
Navedo Manuel F
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1281.8
Subject(s) - bk channel , vascular smooth muscle , diabetes mellitus , medicine , endocrinology , potassium channel , chemistry , smooth muscle
Increased vascular tone and impaired vascular function are major complications during diabetes. Large‐conductance Ca 2+ ‐activated potassium (BK Ca ) channels are important regulators of vascular smooth muscle cell contractility and arterial tone. Whereas multiple reports indicate that BK Ca 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 BK Ca 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 BK Ca channels coupled to Ca 2+ sparks, are significantly decreased in human diabetic cells. Ca 2+ sparks amplitude and frequency was not different between human non‐diabetic and diabetic cells, indicating that impairment in STOC activity occurs at the BK Ca channel level. Consistent with this, BK Ca channels in human diabetic cells showed an apparent reduction in Ca 2+ sensitivity as compared to non‐diabetic cells. These results suggest impaired BK Ca channel function due to aberrant Ca 2+ 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 Information This work was supported by grants NIH‐HL098200 and NIH‐HL121059, and AHA‐14GRNT18730054 to MFN.