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β- and α-adrenergic cross-signaling for L-type Ca current is impaired in transgenic mice with constitutive activation of ϵPKC
- Source :
-
Biochemical & Biophysical Research Communications . Feb2004, Vol. 314 Issue 3, p749. 6p. - Publication Year :
- 2004
-
Abstract
- It is well established that β-adrenoceptor stimulation activates PKA and <f>α1</f>-adrenoceptor stimulation activates PKC. In normal ventricular myocytes, acute activation of <f>α1</f>-adrenoceptors inhibits β-adrenoceptor stimulated L-type Ca current (ICa-L) and direct activation of &epsiv;PKC leads to ICa-L inhibition. Because increased PKC activity has been observed chronically in in vivo setting such as failing human heart, we hypothesized that chronic in vivo activation of &epsiv;PKC alters ICa-L and its response to adrenergic stimulation. Therefore, we investigated the interaction between β- and <f>α1</f>-adrenoceptors vis-a&grave;-vis ICa-L in myocytes from transgenic mice (TG) with cardiac specific constitutive activation of &epsiv;PKC (&epsiv;PKC agonist). Whole-cell ICa-L was recorded from &epsiv;PKC agonist TG mice and age-matched non-TG (NTG) littermates under: (1) basal condition, (2) β-adrenoceptor agonist, isoproterenol (ISO), and (3) ISO plus <f>α1</f>-adrenoceptor agonist, methoxamine. The present results are the first to demonstrate that chronic in vivo activation of &epsiv;PKC leads to reduced basal ICa-L density. β-adrenoceptor activation of ICa-L is blunted in &epsiv;PKC agonist TG mice. α-adrenoceptor cross-talk with β-adrenoceptor signaling pathways vis-a&grave;-vis L-type Ca channels is impaired in &epsiv;PKC agonist TG mice. The diminished response to ISO and methoxamine suggests a protective feedback regulatory mechanism in &epsiv;PKC agonist TG mice and could be vital in the settings of excessive release of catecholamines during heart failure. [Copyright &y& Elsevier]
- Subjects :
- *ADRENERGIC receptors
*MUSCLE cells
*HEART diseases
Subjects
Details
- Language :
- English
- ISSN :
- 0006291X
- Volume :
- 314
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Biochemical & Biophysical Research Communications
- Publication Type :
- Academic Journal
- Accession number :
- 11960362
- Full Text :
- https://doi.org/10.1016/j.bbrc.2003.12.155