Interactions of PPARα and Acid Sensing Ion Channels on Cerebral Perfusion in Mice

Abstract

Acid sensing ion channels (ASICs) are expressed in the brain and are made up of various proton sensitive channels which play critical roles in cellular physiology. Different genes have been shown to code for these channels. PPARα, a nuclear transcription factor that regulates many genes is also expressed in the brain and may have a regulatory role in the functions of ASICs. We have investigated the effects of interactions of PPARα and ASICs on the regulation of cerebral perfusion (CP) in mice. Anesthetized wild type (WT) or PPARα knockout (KO) mice received Amiloride (A), ENaC blocker, Benzamil (B), inhibitor of ENaC and Na+/Ca2+ exchange (NCX) blocker; Furosemide (F), inhibitor of Na‐K‐2Cl symporter, or Nigericin (N), ionophore and antiporter of H+ and K+(0.020, 0.35, 6.25, 0.025 mg/kg, respectively). Effects of the treatments were determined by Laser Doppler Scanner (Moor LDI 5152). CP was increased in the WT by 23, 38, or 26% and was attenuated in the KO to −6, 13, or 11% (A, p<0.05), B increased CP in the WT to 24, 38, or 28% and was attenuated to −1, 17, 28% (p>0.05) at 10, 30, or 60 min, respectively (n=3–5, ANOVA). Treatment with F or N reduced CP in the WT and the KO to similar extent. These data indicate that ASICs selectively sensitive to Amiloride and Benzamil are involved in maintaining basal brain perfusion and that PPARα gene is involved. The mechanism for such regulation needs further investigation.