Diabetes Upregulates <scp> BK _Ca </scp> Channels in Pulmonary Arterial Smooth Muscle by Altering the Local Control Mechanism of the Pore‐Gate Domain

ABSTRACT Objective Large conductance calcium‐activated potassium channels (BK Ca ) play an important role in the regulation of vascular tone. However, the properties of BK Ca channels in smooth muscle of pulmonary arteries are poorly understood. Previous experimental studies demonstrated that pulmonary hypoxic vasoconstriction as a normal physiological response to decreased oxygen levels was impaired in diabetic animals due to abnormal activation of BK Ca channels. The aim of this study was to identify mechanisms of diabetes‐induced activation of BK Ca channels in freshly isolated smooth muscle cells from rat pulmonary arteries. Methods Type 1 diabetes was induced by streptozotocin (STZ). Whole‐cell potassium currents were recorded using the patch‐clamp method. Expression levels of BK‐α and BK‐β1 subunits were measured by real‐time PCR. Results Our results demonstrate that the amplitude of whole‐cell current through BK Ca channels in rat pulmonary artery smooth muscle cells is significantly increased during STZ‐induced diabetes without altering the expression of BK‐α and BK‐β1 subunits and channel calcium sensitivity. The slow component of BK Ca current deactivation time constant and spontaneous transient outward current amplitude were increased in diabetic animals compared to healthy animals. Conclusions We conclude that abnormal activation of the BK Ca channel in pulmonary arterial smooth muscle during diabetes is associated with alterations in the local control mechanism of the BK Ca pore‐gate domain.