Slowing of the inactivation of voltage-dependent sodium channels by staurosporine, the protein kinase C inhibitor, in rabbit atrial myocytes

Jae Hong Ko, Won Sun Park, Sungjoon Kim, Yung E. Earm

Research output: Contribution to journalArticleResearchpeer-review

9 Citations (Scopus)

Abstract

In this study, the effect of staurosporine, a potent protein kinase C (PKC) inhibitor, on Na+ current (INa) was examined by whole-cell patch recording in rabbit atrial myocytes. The most prominent staurosporine effect was a slowing of INa inactivation and 1 μM staurosporine reduced amplitude of INa about 33%. Staurosporine decreased INa at all potentials and slowed the INa inactivation in a dose-dependent manner, with a Kd value of 1.107 ± 0.162 μM. Staurosporine did not change the recovery kinetics and show use dependence. However, the activation and the steady-state inactivation curves were shifted toward more negative potentials (- 5.5 and - 5.1 mV, respectively). Two other PKC inhibitors, GF 109203X (1 μM) and chelerythrine (3 μM), did not show a slowing effect on INa inactivation. In conclusion, our results indicate that the slowing of INa inactivation by staurosporine seems not to be through blockade of PKC rather to act directly on the Na+ channels, and the direct blocking effects of staurosporine on the Na+ channel should be taken into consideration when staurosporine is used in functional studies of ion channel modulation by protein phosphorylation.

Original languageEnglish
Pages (from-to)48-54
Number of pages7
JournalEuropean Journal of Pharmacology
Volume534
Issue number1-3
DOIs
StatePublished - 18 Mar 2006

Fingerprint

Staurosporine
Protein C Inhibitor
Sodium Channels
Protein Kinase Inhibitors
Muscle Cells
Protein Kinase C
Rabbits
Patch-Clamp Techniques
Ion Channels
Phosphorylation

Keywords

  • Atrial myocyte
  • Na current (I)
  • Protein kinase C
  • Staurosporine

Cite this

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title = "Slowing of the inactivation of voltage-dependent sodium channels by staurosporine, the protein kinase C inhibitor, in rabbit atrial myocytes",
abstract = "In this study, the effect of staurosporine, a potent protein kinase C (PKC) inhibitor, on Na+ current (INa) was examined by whole-cell patch recording in rabbit atrial myocytes. The most prominent staurosporine effect was a slowing of INa inactivation and 1 μM staurosporine reduced amplitude of INa about 33{\%}. Staurosporine decreased INa at all potentials and slowed the INa inactivation in a dose-dependent manner, with a Kd value of 1.107 ± 0.162 μM. Staurosporine did not change the recovery kinetics and show use dependence. However, the activation and the steady-state inactivation curves were shifted toward more negative potentials (- 5.5 and - 5.1 mV, respectively). Two other PKC inhibitors, GF 109203X (1 μM) and chelerythrine (3 μM), did not show a slowing effect on INa inactivation. In conclusion, our results indicate that the slowing of INa inactivation by staurosporine seems not to be through blockade of PKC rather to act directly on the Na+ channels, and the direct blocking effects of staurosporine on the Na+ channel should be taken into consideration when staurosporine is used in functional studies of ion channel modulation by protein phosphorylation.",
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Slowing of the inactivation of voltage-dependent sodium channels by staurosporine, the protein kinase C inhibitor, in rabbit atrial myocytes. / Ko, Jae Hong; Park, Won Sun; Kim, Sungjoon; Earm, Yung E.

In: European Journal of Pharmacology, Vol. 534, No. 1-3, 18.03.2006, p. 48-54.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Slowing of the inactivation of voltage-dependent sodium channels by staurosporine, the protein kinase C inhibitor, in rabbit atrial myocytes

AU - Ko, Jae Hong

AU - Park, Won Sun

AU - Kim, Sungjoon

AU - Earm, Yung E.

PY - 2006/3/18

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N2 - In this study, the effect of staurosporine, a potent protein kinase C (PKC) inhibitor, on Na+ current (INa) was examined by whole-cell patch recording in rabbit atrial myocytes. The most prominent staurosporine effect was a slowing of INa inactivation and 1 μM staurosporine reduced amplitude of INa about 33%. Staurosporine decreased INa at all potentials and slowed the INa inactivation in a dose-dependent manner, with a Kd value of 1.107 ± 0.162 μM. Staurosporine did not change the recovery kinetics and show use dependence. However, the activation and the steady-state inactivation curves were shifted toward more negative potentials (- 5.5 and - 5.1 mV, respectively). Two other PKC inhibitors, GF 109203X (1 μM) and chelerythrine (3 μM), did not show a slowing effect on INa inactivation. In conclusion, our results indicate that the slowing of INa inactivation by staurosporine seems not to be through blockade of PKC rather to act directly on the Na+ channels, and the direct blocking effects of staurosporine on the Na+ channel should be taken into consideration when staurosporine is used in functional studies of ion channel modulation by protein phosphorylation.

AB - In this study, the effect of staurosporine, a potent protein kinase C (PKC) inhibitor, on Na+ current (INa) was examined by whole-cell patch recording in rabbit atrial myocytes. The most prominent staurosporine effect was a slowing of INa inactivation and 1 μM staurosporine reduced amplitude of INa about 33%. Staurosporine decreased INa at all potentials and slowed the INa inactivation in a dose-dependent manner, with a Kd value of 1.107 ± 0.162 μM. Staurosporine did not change the recovery kinetics and show use dependence. However, the activation and the steady-state inactivation curves were shifted toward more negative potentials (- 5.5 and - 5.1 mV, respectively). Two other PKC inhibitors, GF 109203X (1 μM) and chelerythrine (3 μM), did not show a slowing effect on INa inactivation. In conclusion, our results indicate that the slowing of INa inactivation by staurosporine seems not to be through blockade of PKC rather to act directly on the Na+ channels, and the direct blocking effects of staurosporine on the Na+ channel should be taken into consideration when staurosporine is used in functional studies of ion channel modulation by protein phosphorylation.

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