Figure 2. Mechanism of modifying TREK-1 current in rest and during stress.

(A) Mechanism by which Popdc1 and Popdc2 induce a TREK-1 outward current in resting conditions, as suggested by the work of Froese and colleagues (8). Note that we believe it is possible that Popdc1 and Popdc2 also interact with Scn5a or Ankyrin-B. (B) Increased levels of cAMP induced by β-adrenergic receptor stimulation cause Popdc1 or Popdc2 to release TREK-1, resulting in inhibition of the TREK-1 outward current. This mechanism is absent in mice mutant for either Popdc1 or Popdc2, and therefore TREK-1 current is chronically reduced.