α1-Adrenoceptors stimulate a Gαsprotein and reduce the transient outward K+current via a cAMP/PKA-mediated pathway in the rat heart
| Autor: | María del Carmen Boyano-Adánez, Raúl Setién, Eduardo Arilla, Lilian Puebla, Oscar Casis, Mónica Gallego |
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| Rok vydání: | 2005 |
| Předmět: |
Inotrope
medicine.medical_specialty Patch-Clamp Techniques Potassium Channels Gs alpha subunit Physiology Stimulation Biology Rats Sprague-Dawley Norepinephrine Phenylephrine Receptors Adrenergic alpha-1 Internal medicine Cyclic AMP GTP-Binding Protein alpha Subunits Gs medicine Animals Myocytes Cardiac Cells Cultured Myocardium Cell Membrane Colforsin Cardiac action potential Cell Biology Rat heart Compartmentalization (fire protection) Cyclic AMP-Dependent Protein Kinases α1 adrenoceptor Rats Cell biology Endocrinology Type C Phospholipases Calcium-Calmodulin-Dependent Protein Kinases Circulatory system Potassium Calcium-Calmodulin-Dependent Protein Kinase Type 2 Adrenergic alpha-Agonists Signal Transduction |
| Zdroj: | American Journal of Physiology-Cell Physiology. 288:C577-C585 |
| ISSN: | 1522-1563 0363-6143 |
| Popis: | α1-Adrenoceptor stimulation prolongs the duration of the cardiac action potentials and leads to positive inotropic effects by inhibiting the transient outward K+current ( Ito). In the present study, we have examined the role of several protein kinases and the G protein involved in Itoinhibition in response to α1-adrenoceptor stimulation in isolated adult rat ventricular myocytes. Our findings exclude the classic α1-adrenergic pathway: activation of the G protein Gαq, phospholipase C (PLC), and protein kinase C (PKC), because neither PLC, nor PKC, nor Gαqblockade prevents the α1-induced Itoreduction. To the contrary, the α1-adrenoceptor does not inhibit Itoin the presence of protein kinase A (PKA), adenylyl cyclase, or Gαsinhibitors. In addition, PKA and adenylyl cyclase activation inhibit Itoto the same extent as phenylephrine. Finally, we have shown a functional coupling between the α1-adrenoceptor and Gαsin a physiological system. Moreover, this coupling seems to be compartmentalized, because the α1-adrenoceptor increases cAMP levels only in intact cells, but not in isolated membranes, and the effect on Itodisappears when the cytoskeleton is disrupted. We conclude that α1-adrenoceptor stimulation reduces the amplitude of the Itoby activating a Gαsprotein and the cAMP/PKA signaling cascade, which in turn leads to Itochannel phosphorylation. |
| Databáze: | OpenAIRE |
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