In diabetes mellitus, the action of BK channels is reduced,
in part by decreased calcium sensitivity from a reduction in β1
subunit expression.11 Interestingly, the nature of the reduced
activity changes over time. Early in the Zucker high-fat diet–
induced model of diabetes mellitus (8 weeks), vascular dysfunction
and reduced BK currents are observed in VSMCs.12
By 4 to 6 months, BK channels still open to voltage changes
but calcium sensitivity is reduced.13 At this more advanced
stage, the Zucker high-fat diet–induced model of diabetes
mellitus rat also demonstrates abnormal biophysical properties
of the BK channel, not observed at earlier time points, including
impaired calcium sensitivity, more prolonged closed
times, and shortened opening times