This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sun, C. Articles by Raizada, M. K. Search for Related Content PubMed PubMed Citation Articles by Sun, C. Articles by Raizada, M. K. Related Collections Electrophysiology ACE/Angiotension receptors Cell signalling/signal transduction Functional genomics Hypertension - basic studies Ion channels/membrane transport Receptor pharmacology

(Hypertension. 2002;39:562.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Chronotropic Action of Angiotensin II in Neurons via Protein Kinase C and CaMKII

Chengwen Sun; Colin Sumners; Mohan K. Raizada

Department of Physiology and Functional Genomics, College of Medicine & McKnight Brain Institute, University of Florida, Gainesville

Correspondence to Mohan K. Raizada, Department of Physiology and Functional Genomics, University of Florida, College of Medicine, PO Box 100274, Gainesville, FL 32610-0274. E-mail mraizada{at}phys.med.ufl.edu

Angiotensin II (Ang II) plays an important role in the central control of blood pressure and baroreflexes. These effects are initiated by stimulation of Ang II type 1 (AT₁) receptors on neurons within the hypothalamus and brain stem, and involve increasing the activity of noradrenergic, substance P, and glutamatergic pathways. The goal of this study is to investigate the intracellular signaling molecules, which are involved in mediating the Ang II-induced increases in neuronal activity. Using neurons in primary culture from newborn rat hypothalamus and brain stem, we have previously determined that Ang II elicits an AT₁ receptor-mediated inhibition of delayed rectifier K⁺ current, a stimulation of Ca²⁺ current, and a consequent increase in firing rate. In the present study we have demonstrated that this chronotropic action of Ang II in neuronal cultures involves activation of Ca²⁺-dependent signaling molecules. The Ang II-induced increase in firing rate was abolished by inhibition of phospholipase C with U73122 (10 µmol/L), and was attenuated by the protein kinase C inhibitor calphostin C (10 µmol/L) or by the calcium/calmodulin-dependent kinase II (CaMKII) inhibitor KN-93 (10 µmol/L). A combination of calphostin C and KN-93 completely inhibited this Ang II action. These results indicate that the AT₁ receptor-mediated increase in neuronal firing rate involves activation of both PKC and CaMKII, and suggest that these enzymes are potential targets for manipulating the central actions of Ang II.

Key Words: angiotensin II • receptors, angiotensin • protein kinases • rats • nervous system • neuropeptides

This article has been cited by other articles:

				A. Israel, J. Arzola, S. De Jesus, and M. Varela Role of oxidative stress in the natriuresis induced by central administration of angiotensin II Journal of Renin-Angiotensin-Aldosterone System, March 1, 2009; 10(1): 9 - 14. [Abstract] [PDF]

				G. R. Borges, H. C. Salgado, C. A. A. Silva, M. A. Rossi, C. M. Prado, and R. Fazan Jr. Changes in hemodynamic and neurohumoral control cause cardiac damage in one-kidney, one-clip hypertensive mice Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2008; 295(6): R1904 - R1913. [Abstract] [Full Text] [PDF]

				C. Sun, K. W. Sellers, C. Sumners, and M. K. Raizada NAD(P)H Oxidase Inhibition Attenuates Neuronal Chronotropic Actions of Angiotensin II Circ. Res., April 1, 2005; 96(6): 659 - 666. [Abstract] [Full Text] [PDF]

				S. F. Fernandez, M.-H. Huang, B. A. Davidson, P. R Knight III, and J. L. Izzo Jr Mechanisms of Angiotensin II-Mediated Decreases in Intraneuronal Ca2+ in Calcium-Loaded Stellate Ganglion Neurons Hypertension, February 1, 2005; 45(2): 276 - 282. [Abstract] [Full Text] [PDF]

				C. Sun, H. Li, L. Leng, M. K. Raizada, R. Bucala, and C. Sumners Macrophage Migration Inhibitory Factor: An Intracellular Inhibitor of Angiotensin II-Induced Increases in Neuronal Activity J. Neurosci., November 3, 2004; 24(44): 9944 - 9952. [Abstract] [Full Text] [PDF]

				C. Sun, J. Du, C. Sumners, and M. K. Raizada PI3-Kinase Inhibitors Abolish the Enhanced Chronotropic Effects of Angiotensin II in Spontaneously Hypertensive Rat Brain Neurons J Neurophysiol, November 1, 2003; 90(5): 3155 - 3160. [Abstract] [Full Text] [PDF]

				J. Pamidimukkala and M. Hay 17{beta}-Estradiol inhibits angiotensin II activation of area postrema neurons Am J Physiol Heart Circ Physiol, October 1, 2003; 285(4): H1515 - H1520. [Abstract] [Full Text] [PDF]

				M. A. Fleegal and C. Sumners Drinking behavior elicited by central injection of angiotensin II: roles for protein kinase C and Ca2+/calmodulin-dependent protein kinase II Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2003; 285(3): R632 - R640. [Abstract] [Full Text] [PDF]

				J. Vazquez, C. Sun, J. Du, L. Fuentes, C. Sumners, and M. K. Raizada Transduction of a Functional Domain of the AT1 Receptor in Neurons by HIV-Tat PTD Hypertension, March 1, 2003; 41(3): 751 - 756. [Abstract] [Full Text] [PDF]

				H. Yang, S. C. Francis, K. Sellers, M. DeBarros, C. Sun, C. Sumners, C. M. Ferrario, M. J. Katovich, A. F. Muro, and M. K. Raizada Hypertension-Linked Decrease in the Expression of Brain {gamma}-Adducin Circ. Res., October 4, 2002; 91(7): 633 - 639. [Abstract] [Full Text] [PDF]