Inositol 1,4,5‐trisphosphate (IP3) rescued TRPC channel activity from inhibition by phosphatidylinositol 4,5‐bisphosphate (PIP2) in vascular myocytes

Abstract

We have previously shown that PIP2 has a marked inhibitory action on TRPC6 channel activity in rabbit mesenteric artery (Albert et al, 2008). Moreover we proposed that diacylglycerol (DAG) is the activating ligand and that DAG and PIP2 act at similar sites on the channel protein to regulate gating of TRPC6. In the present work we studied interactions between DAG, PIP2 and IP3 on TRPC6‐like channel activity in rabbit portal vein myocytes to investigate potential mechanisms involved in mediating previously described synergism between DAG and IP3 (Albert & Large, 2003).Bath application of PIP2 inhibited TRPC6‐like channel activity induced by the DAG analogue, OAG, in inside‐out patches. These data indicate that PIP2 has a similar inhibitory action on TRPC6‐like activity in portal vein as on TRPC6 activity in mesenteric artery. Interestingly, bath application of IP3 in the presence of PIP2 rescued inhibition of OAG‐evoked TRPC6‐like activity in inside‐out patches. Moreover anti‐TRPC6 and ‐TRPC7 antibodies inhibited channel activity suggesting cation channels in portal vein are composed of TRPC6/TRPC7 heterotetrameric structures. These results may indicate that IP3 potentiation of TRPC channel is mediated by TRPC7 proteins.Albert & Large (2003) J Physiol 552, 798‐95; Albert et al (2008) J Physiol 586 3087‐95