Figure 6.

The Ca²⁺ ionophore A23187 is a competitive agonist of TRPM4. Skeletal muscle (m. gracilis) arteries were isolated from the rat and the changes in vascular diameter were recorded upon 9-phenanthrol addition into the organ bath (Panel A,B, n = 5). Note, 9-phenanthrol had no effects at a concentration of 100 nM (maintained myogenic tone and vascular diameter, panel A), while it resulted in a loss of myogenic tone (and in an increased diameter) at higher (shown at 10 µM) concentrations (Panel B). In individual arteries, the effects of 9-phenanthrol (applied concentrations are labeled) on A23187-evoked vasoconstrictions were also tested (Panel C). The apparent EC50 values were plotted on a Schild plot (Panel D) to yield the stability constant of 9-phenanthrol to bind to the A23187 binding sites in vascular preparations. Note, these results implicated a common receptor for 9-phenanthrol and A23187 (e.g., TRPM4) in this system. Twenty (n = 20) animals were used for these studies.