Activation of PKC increases Na + -K + pump current in ventricular myocytes from guinea pig heart
Autor: | Ira S. Cohen, Junyuan Gao, Richard T. Mathias, Xiurong Sun, G J Baldo, Y. Wang |
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Rok vydání: | 1999 |
Předmět: |
Agonist
medicine.medical_specialty Patch-Clamp Techniques Physiology medicine.drug_class Heart Ventricles Guinea Pigs Clinical Biochemistry In Vitro Techniques Membrane Potentials chemistry.chemical_compound Physiology (medical) Internal medicine medicine Animals Ventricular Function Staurosporine Patch clamp Na+/K+-ATPase Protein kinase A Protein Kinase C Protein kinase C Activator (genetics) business.industry Myocardium Heart Electric Stimulation Electrophysiology Enzyme Activation Endocrinology chemistry Phorbol Tetradecanoylphorbol Acetate Calcium Sodium-Potassium-Exchanging ATPase business Algorithms medicine.drug |
Zdroj: | Pfl�gers Archiv European Journal of Physiology. 437:643-651 |
ISSN: | 1432-2013 0031-6768 |
DOI: | 10.1007/s004240050828 |
Popis: | We have previously shown activation of alpha1-adrenergic receptors increases Na+-K+ pump current (Ip) in guinea pig ventricular myocytes, and the increase is eliminated by blockers of phosphokinase C (PKC). In this study we examined the effect of activators of PKC on Ip. Phorbol 12-myristate 13-acetate (PMA), a PKC activator, increased IP at each test potential without shifting its voltage dependence. The concentration required for a half-maximal response (K0.5) was 6 microM at 15 nM cytosolic [Ca2+] ([Ca2+]i) and 13 nM at 314 nM [Ca2+]i. The maximal increase at either [Ca2+]i was about 30%. Another activator of PKC, 1, 2-dioctanoyl-sn-glycerol (diC8), increased Ip similarly. The effect of PMA on IP was eliminated by the PKC inhibitor staurosporine, but not by the peptide PKI, an inhibitor of protein kinase A (PKA). PMA and alpha1-adrenergic agonist effects both were sensitive to [Ca2+]i, blocked by PKC inhibitors, unaffected by PKA inhibition, and increased Ip uniformly at all voltages. However, they differed in that alpha1-activation caused a maximum increase of 15% vs 30% via PMA, and alpha1-effects were less sensitive to [Ca2+]i than PMA effects. These results demonstrate that activation of PKC causes an increase in Ip in guinea pig ventricular myocytes. Moreover, they suggest that the coupling of alpha1-adrenergic activation to Ip is entirely through PKC, however alpha1-activation may be coupled to a specific population of PKC whereas PMA is a more global agonist. |
Databáze: | OpenAIRE |
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