The K2P channel, TRAAK; expression and function in cerebral arteries

Abstract

The two-pore domain potassium channel (K2P), TRAAK, was previously thought to be expressed only in neurons. We recently demonstrated that arachidonic acid (AA) stimulated K currents in isolated cerebrovascular smooth muscle cells (SMC) and dilated rat middle cerebral arteries (MCA) through an atypical K channel, possibly a K2P channel such as TRAAK. Subsequently, we found that TRAAK is expressed in rat and mouse cerebral arteries. Immunoblotting revealed that TRAAK protein is present in the rat MCA, basilar artery, carotid artery, and aorta. Immuostaining in the MCA of rats and mice demonstrated TRAAK protein in SMC layers. TRAAK mRNA was also found in isolated rat MCA SMC. Using whole cell patch clamping in the presence of 10 mM TEA to inhibit classical K channels, the TRAAK activator trichloroethanol (TCE) elicited large K currents in isolated rat MCA SMC. In addition, TCE dilated denuded, isolated, pressurized, and perfused MCAs in a concentration-dependent manner. In control vessels, 10-2 M TCE caused 48±5% dilation. In the presence of 40 mM KCl to block K efflux, dilation to 10-2 M TCE reached only 20±5%. An inhibitory cocktail of 100 μM Ba, 10 mM TEA, 3 mM 4-AP, and 10 μM glybenclamide to block classical K channels failed to inhibit dilation to TCE. The anesthetic, isoflurane, did not dilate the rat MCA suggesting that the K2P channel, TREK, is not mediating responses to TCE in rat the MCA. In summary, TRAAK is expressed in rodent cerebral and peripheral arteries. Experiments in isolated cerebrovascular SMCs, and in isolated MCAs, indicate that an atypical K channel characteristic of TRAAK is functional in rat cerebral arteries. These data suggest that the dilator response of rat MCAs to AA may be due to activation of TRAAK.