MODULATION OF K-II TYPE 1A RECEPTOR PEPTIDE( AND CA2+ CURRENTS IN CULTURED NEURONS BY AN ANGIOTENSIN)

Angiotensin II (ANG II) inhibits delayed rectifier K+ current (I-K) an d stimulates total Ca2+ current (I-Ca) in neurons cocultured from newb orn rat hypothalamus and brain stem, effects mediated via ANG II type I (ATI) receptors. Here, we identify potential G protein activator reg ions of the AT(1) receptor responsible for initiating the intracellula r changes that lead to alterations in these currents. Intracellular ap plication into cultured neurons of a peptide corresponding to the thir d cytoplasmic loop of the AT(1) receptor (AT(1a/i3)) mimicked the acti ons of ANG IT on I-K and I-Ca, whereas application of a peptide corres ponding to the second cytoplasmic loop (AT(1a/i2)) did not alter these currents. This modulation of I-K and I-Ca by AT(1a/i3) involves intra cellular messengers (G alpha q, protein kinase C, and intracellular Ca 2+) that are identical to those involved in the modulation of I-K and I-Ca following ANG II activation of AT(1) receptors. These data provid e functional evidence for a role of the third cytoplasmic loop of the AT(1) receptor in G protein coupling and subsequent modulation of ion channel effectors.