Modulation of delayed rectifier potassium current by angiotensin II in CATH.a cells.
Angiotensin II (Ang II) modulates, via Ang II type 1 (AT(1)) receptors, the activity of brain catecholaminergic neurons. Here we utilized catecholaminergic CATH.a cells to define the effects of Ang II on delayed rectifier K(+) current (I(Kv)), one of the factors that determines changes in neuronal activation. Receptor binding analyses demonstrated the presence of AT(1) receptors in CATH.a cells. Whole cell voltage clamp experiments in these cells revealed that Ang II (100nM) produced a significant inhibition of I(Kv), that was abolished by the AT(1) receptor blocker, losartan (1 microM), or by inhibition of phospholipase C (PLC) with U73122 (10 microM). Furthermore, this action of Ang II was completely abolished by co-inhibition of protein kinase C (PKC) and calcium/calmodulin protein kinase II (CaMKII). These results demonstrate that Ang II produces an inhibition of I(Kv) in CATH.a cells, via an intracellular pathway that includes PLC, PKC, and CaMKII.
Sun
Chengwen
C
Department of Physiology and Functional Genomics and McKnight Brain Institute, University of Florida, Gainesville 32610, USA.
Du
Jiangqing
J
Raizada
Mohan K
MK
Sumners
Colin
C
D000804:Angiotensin II / Q000096:biosynthesis*; D000818:Animals; D001921:Brain / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D051668:Delayed Rectifier Potassium Channels; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011485:Protein Binding; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D051668:Delayed Rectifier Potassium Channels; D004791:Enzyme Inhibitors; D004963:Estrenes; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011760:Pyrrolidinones; D000804:Angiotensin II; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010738:Type C Phospholipases