Effect of angiotensin II type 1 receptor on delayed rectifier potassium current in catecholaminergic CATH.a cells.
OBJECTIVE
To study the modulatory effects of angiotensin II (Ang II) on the delayed rectifier potassium (Kv) current (IKv) and its underlying intracellular mechanism in the catecholaminergic system of rats.


METHODS
AT1 and AT2 receptors of the differentiated and undifferentiated CATH.a cells were determined by radioligands binding assay. The IKv was recorded with the whole cell patch-clamp configuration in voltage clamp mode on CATH.a cells.


RESULTS
The Ang II receptor proteins including AT1 and AT2 receptors were expressed in CATH.a cells, and the number of the former was significantly more than the latter (P<0.01). The IKv of CATH.a cells was reduced by superfusion with the Ang II (100 nmol/L) (P<0.05) in the presence of the AT2 receptor antagonist PD123319, but was not affected by only superfusion with PD123319. The effect of Ang II on IKv in CATH.a cells was completely inhibited by addition of AT1 receptor antagonist losartan. Superfusion with Ang II (100 nmol/L) plus U73122, an inhibitor of phospholipase C (PLC) in the presence of PD123319 had no effect on the IKv [(20.2+/-2.8) pA/pF]. Ang II-induced reduction of IKv was attenuated (P<0.05) but not abolished by PKC inhibitor calphostin C (Cal) and selective CaMK II inhibitor KN-93 (10 micromol/L) respectively. However, IKv reduction was completely abolished by superfusion with both Cal and KN-93.


CONCLUSIONS
The inhibition of Kv currents in CATH.a cells by Ang II is mediated by AT1 receptor, and the PLC, PKC and CaMK II may be involved in signal transduction of AT1 receptor. The differentiated CATH.a cell is a useful cell model to study Ang II receptor-mediated functional modulation of catecholaminergic system.
Du
Jian-Qing
JQ
Department of Physiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China. jianqingdu@yahoo.com.cn
Sun
Cheng-Wen
CW
Tang
Jing-Shi
JS
D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002395:Catecholamines / Q000502:physiology; D002460:Cell Line; D051668:Delayed Rectifier Potassium Channels; D007093:Imidazoles / Q000494:pharmacology; D008125:Locus Coeruleus / Q000166:cytology / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology; D051379:Mice; D009281:Naphthalenes; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D000096926:Benzenesulfonamides
D000804:Angiotensin II; D047228:Angiotensin II Type 1 Receptor Blockers; D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002395:Catecholamines; D051668:Delayed Rectifier Potassium Channels; D007093:Imidazoles; D019808:Losartan; D009281:Naphthalenes; D024642:Potassium Channels, Voltage-Gated; D011493:Protein Kinase C; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013449:Sulfonamides; D010738:Type C Phospholipases; C073402:PD 123319; C072105:KN 93; D000096926:Benzenesulfonamides; C058819:calphostin C