Presenter : Michaeli Francisco
Poster 9
Tetraethylammonium (TEA) abolishes a large portion of the vasodilation observed with both cutaneous thermal and reactive hyper- emia by blocking calcium-sensitive potassium (KCa) channels. Some studies have shown effects of TEA on other potassium channels such as inward-rectifying potassium (KIR) channels, which are activated by increases in extracellular K+ and blocked by barium (Ba2+). Our primary goal was to test the specificity of TEA to KCa channels by ensuring TEA had no effect on KIR-mediated vaso- dilation to KCl. Furthermore, the effects of KIR channels in the skin has not previously been explored. Recent research suggests KIR channel activation to be the predominant contributor to ATP-mediated dilation in the forearm. Therefore, our secondary goal was to assess KIR-mediated vasodilation in response to ATP. The following drugs were continuously infused via microdialysis: 1) Control; 2) 50mM TEA; 3) 0.1mM barium chloride (BaCl2; KIR channel blocker). KCl was infused for 2 min at each site at 1mM and 10mM doses. Following KCl infusions, a single dose of 30mM ATP was infused for 1 min at each site. Dilation was characterized as Δ peak from baseline, and presented as % maximal cutaneous vascular conductance (CVC). KCl mediated vasodilation at the control site (1mM: 11.0±2.7%, 10mM: 10.4±2.3%) indicated 1mM KCl is sufficient to achieve complete activation of KIR channels, which is only ~ 10% of max. TEA had little effect on KCl-mediated vasodilation (1mM: 7.2.0±2.2%, 10mM: 9.2±3.1%) suggesting TEA does not affect KIR and/or Na+/K+ATPase pumps. Dilation to KCl was attenuated but not blocked by 0.1mM BaCl2 (1mM KCl: 6.0±1.7%, 10mM KCl: 4.9±2.0%). This indicates Na+/K+ATPase could also be responsible for a large portion of KCl-mediated vasodilation in the skin. ATP-mediated vasodilation was largely independent of KIR channel activation (Control: 43.7±14.0%, BaCl2: 41.0±11.4%). However, TEA blocked a large portion of ATP-mediated dilation (TEA: 11.6±4.5%) implicating KCa channels as a primary mechanism in ATP- mediated vasodilation in the skin.