Studies were performed to assess whether ATP-sensitive K+ (K(ATP)) channels on rabbit preglomerular vessels can influence afferent arteriolar (AA) tone. K+ channels with a slope conductance of 258±13 (n = 7) pS and pronounced voltage dependence were demonstrated in excised patches from vascular smooth muscle cells of microdissected preglomerular segments. Channel activity was markedly reduced by 1 mM ATP and in a dose-dependent fashion by glibenclamide (10-9 M to 10-6 M), a specific antagonist of K(ATP) channels. 10-5 M diazoxide, a K+ channel opener, activated these channels in the presence of ATP, and this effect was also blocked by glibenclamide. To determine the role of these K(ATP) channels in the control of vascular tone, diazoxide was tested on isolated perfused AA. After preconstriction from a control diameter of 13.1±1.1 to 3.5±2.1 μm with phenylephrine (PE), addition of 10-5 M diazoxide dilated vessels to 11.2±0.7 μm, which was not different from control. Further addition of 10- 5 M glibenclamide reconstricted the vessels to 5.8±1.5 μm (n = 5; P < 0.03). In support of its specificity for K(ATP) channels, glibenclamide did not reverse verapamil induced dilation in a separate series of experiments. To determine whether intracellular ATP levels can effect AA tone, studies were conducted to test the effect of the glycolytic inhibitor 2-deoxy-D- glucose. After preconstriction from 13.4±3.2 to 7.7±1.3 μm with PE, bath glucose was replaced with 6 mM 2-deoxy-D-glucose. Within 10 min, the arteriole dilated to a mean value of 11.8±1.4 μm (n = 6; NS compared to control). Subsequent addition of 10-5 M glibenclamide significantly reconstricted the vessels to a diameter of 8.6±0.5 μm (P < 0.04). These data demonstrate that K(ATP) channels are present on the preglomerular vasculature and that changes in intracellular ATP can directly influence afferent arteriolar tone via these channels.
- patch clamp
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