Medizinische Universität Graz - Research portal
Selected Publication:
Schreibmayer, W; Frohnwieser, B; Dascal, N; Platzer, D; Spreitzer, B; Zechner, R; Kallen, RG; Lester, HA.
Beta-adrenergic modulation of currents produced by rat cardiac Na+ channels expressed in Xenopus laevis oocytes.
Receptors Channels. 1994; 2(4):339-350
Web of Science
PubMed
- Leading authors Med Uni Graz
- Schreibmayer Wolfgang
- Co-authors Med Uni Graz
- Platzer Dieter
- Steinecker-Frohnwieser Bibiane
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- Abstract:
- In Xenopus oocytes coexpressing beta 2-adrenergic receptors and the rat cardiac alpha SkM2 Na+ channel, superfusion with 10 microM isoproterenol led to modest (approximately 30%) increases in peak Na+ inward current. Intracellular injection of cAMP and of protein kinase A (PKA) catalytic subunit reproduced this increase, showing that the second messenger pathway involves PKA dependent phosphorylation. Coexpression of the Na+ channel beta 1 subunit had no influence on the modulation. The modulation had little or no effect upon Na+ current waveforms, steady-state activation, steady-state activation, steady-state inactivation, or recovery from both fast and slow inactivation; but maximum Na+ conductance was increased. Mutation of the five major consensus PKA phosphorylation sites on alpha SkM2 did not abolish the observed effect. In parallel experiments, beta-adrenergic stimulation of the neuronal alpha IIA Na+ channel subunit led to an attenuation of Na+ current. It is concluded that (i) the alpha SkM2 subunit might be directly phosphorylated by PKA, but at serine/threonine residue(s) in a cryptic phosphorylation site(s); or that (ii) the modulation might also be mediated by phosphorylation of another, as yet unknown protein(s). The divergent modulation of neuronal and cardiac Na+ channel alpha-subunits suggests that differential physiological modulation by identical second messenger pathways is the evolutionary basis for the isoform diversity within this protein family.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Base Sequence -
- Cell Membrane - drug effects Cell Membrane - physiology
- Chloride Channels - physiology
- Cyclic AMP - metabolism Cyclic AMP - pharmacology
- Cyclic AMP-Dependent Protein Kinases - metabolism
- Cystic Fibrosis Transmembrane Conductance Regulator -
- Female -
- Heart - physiology
- Humans -
- Isoproterenol - pharmacology
- Membrane Proteins - drug effects Membrane Proteins - physiology
- Molecular Sequence Data -
- Mutagenesis, Site-Directed -
- Myocardium - metabolism
- Oligodeoxyribonucleotides -
- Oocytes - drug effects Oocytes - physiology
- Rats -
- Receptors, Adrenergic, beta-2 - biosynthesis Receptors, Adrenergic, beta-2 - physiology
- Recombinant Proteins - biosynthesis Recombinant Proteins - drug effects Recombinant Proteins - metabolism
- Second Messenger Systems -
- Sodium Channels - biosynthesis Sodium Channels - drug effects Sodium Channels - physiology
- Xenopus laevis -
- Find related publications in this database (Keywords)
- G PROTEINS
- HEART
- HETEROLOGOUS EXPRESSION