Author + information
- Wen Jing and
- Yang Yan
The large conductance calcium-activated potassium channels (BKCa) dysfunction occurs in several vascular diseases including hypertension. Nitric Oxide (NO) is an endothelium-independent relaxant agent and also one of the important cellular messengers to regulate the function of cardiovascular system. The effect of NO on BKCa in human artery SMCs during hypertension is rarely studied. The aim of present study was to investigate whether the change of NO on BKCa channels during hypertension.
The use of sodium nitroprusside (SNP) as NO donor in solutions was utilized. The freshly isolated SMCs were used to record BKCa currents using the patch-clamp technique.
(1) In cell-attached patch (Vm = + 40 mV), 100μM SNP stimulates BKCa activity significantly in the normotensive patients (NT group): NO enhanced BKCa open probability(NPo), from 0.007±0.002 to 0.018±0.006, the mean open time (To) of BKCachannels was increased from (6.128 ± 1.003) ms to (12.532±2.031) ms, and the mean close time (Tc) of BKCa channels was reduced from (1486.862±246.189) ms to (806.327 ± 193.261) ms (n=8, P<0.05). In the hypertensive patients (HT group), NOhad no significant effect on BKCa. (2) In inside-out patch (Vm=+40 mV), application of SNP, NPo of BKCa channel was increased from 0.006 ± 0.001 to 0.015±0.003, To of BKCa channels was increased from (5.963±0.821) ms to (11.972±1.782) ms, andTc of BKCa channels was reduced from (1648.634±367.326) ms to (753.017±258.148) ms (n=7, P <0.05). In the HT group, NO had no significant effect on BKCa.(3) In the amphotericin-perforated whole-cell patch-clamp configuration, the current densityof BKCa in the NT group at the voltage of -60∼ +20 mV had no significant change after adding 100μM SNP, but the current density of BKCa at the voltage of + 30 mV, + 40 mV, + 50 mV and + 60 mV was increased significantly, from 11.352±1.256 pA/pF, 16.633 ±1.841 pA/pF, 22.4227±1.287 pA/pF and 29.434±1.346 pA/pF to 15.530±1.339 pA/pF, 22.517±1.463 pA/pF, 31.672±1.438 pA/pF and 45.657±2.981 pA/pF (n=7, P<0.05). In the HT group, AngII had no significant effect on macroscopic current of BKCa channels.
Our results suggested that NO can activate BKCa channels of human mesenteric artery SMCs. Furthermore, the sensitivity of BKCa channels to NO is significantly lowered during hypertension.