Activation of Endothelial Cell BK Channels by the Gasotransmitter Hydrogen Sulfide

Hydrogen sulfide can function as a preconditioning stimulus by preventing leukocyte‐endothelial cell (EC) interactions following ischemia‐reperfusion injury in the intestinal wall. The actions of H 2 S are prevented by paxilline, an inhibitor of large‐conductance, Ca 2+ ‐activated K + (BK) channels. Using whole‐cell and single‐channel patch clamp methods, we tested the hypothesis that H 2 S directly activates BK channels in ECs. Human microvascular endothelial cells (HMECs) were plated on glass coverslips and voltage‐clamped under conditions favorable for recording K + current. In whole‐cell mode, depolarizing steps from a holding potential of −70 mV resulted in robust, Ca 2+ ‐sensitive K + currents that were inhibited by IBTX (100 nM). Likewise, excised, inside‐out membrane patches exhibited outward, Ca 2+ ‐ and IBTX‐sensitive K + currents at positive potentials in the presence of IK/SK channel blockers. Bath application of NaHS (100 μM) increased whole‐cell K + current by 1.5–2.0 fold and significantly increased the N•Po of single channel K + currents; these NaHS actions were prevented by IBTX. These results are consistent with a role for EC BK channels in the preconditioning effect of H 2 S.