Inhibition of Kv1.3 channels by H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide) independent of protein kinase A

Jin Sung Choi; Bok Hee Choi; Sang June Hahn; Shin Hee Yoon; Do Sik Min; Yang Hyeok Jo; Myung Suk Kim

doi:10.1016/S0006-2952(01)00556-1

Inhibition of Kv1.3 channels by H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide) independent of protein kinase A

Jin Sung Choi, Bok Hee Choi, Sang June Hahn, Shin Hee Yoon, Do Sik Min, Yang Hyeok Jo, Myung Suk Kim

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

Abstract

The effects of H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide), a potent and selective inhibitor of protein kinase A (PKA), were examined on Kv1.3 channels stably expressed in Chinese hamster ovary (CHO) cells using the patch clamp technique. In whole-cell recordings, H-89 decreased Kv1.3 currents and accelerated the decay rate of current inactivation in a concentration-dependent manner with an ic₅₀ value of 1.70 μM. These effects were completely reversible after washout. Intracellular infusion with PKA inhibitors, adenosine 3′, 5′-cyclic phosphorothioate-Rp (Rp-cAMPS) or protein kinase A inhibitor 5-24 (PKI 5-24) had no effect on Kv1.3 currents and did not prevent the inhibitory action of H-89 on the current. H-89 applied to the cytoplasmic surface also inhibited Kv1.3 currents in excised inside-out patches. These findings suggest that H-89 inhibits Kv1.3 currents independently of PKA.

Original language	English
Pages (from-to)	1029-1032
Number of pages	4
Journal	Biochemical Pharmacology
Volume	61
Issue number	8
DOIs	https://doi.org/10.1016/S0006-2952(01)00556-1
Publication status	Published - 2001 Apr 15

Bibliographical note

Funding Information:
We thank Dr. Kaczmarek (Yale University School of Medicine, USA) for the Kv1.3 transfected CHO cells and Won Kim for reading the manuscript. This work was supported by the Catholic Medical Center Research Fund for Special Projects (1997).

All Science Journal Classification (ASJC) codes

Biochemistry
Pharmacology

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10.1016/S0006-2952(01)00556-1

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title = "Inhibition of Kv1.3 channels by H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide) independent of protein kinase A",

abstract = "The effects of H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide), a potent and selective inhibitor of protein kinase A (PKA), were examined on Kv1.3 channels stably expressed in Chinese hamster ovary (CHO) cells using the patch clamp technique. In whole-cell recordings, H-89 decreased Kv1.3 currents and accelerated the decay rate of current inactivation in a concentration-dependent manner with an ic50 value of 1.70 μM. These effects were completely reversible after washout. Intracellular infusion with PKA inhibitors, adenosine 3′, 5′-cyclic phosphorothioate-Rp (Rp-cAMPS) or protein kinase A inhibitor 5-24 (PKI 5-24) had no effect on Kv1.3 currents and did not prevent the inhibitory action of H-89 on the current. H-89 applied to the cytoplasmic surface also inhibited Kv1.3 currents in excised inside-out patches. These findings suggest that H-89 inhibits Kv1.3 currents independently of PKA.",

author = "Choi, {Jin Sung} and Choi, {Bok Hee} and Hahn, {Sang June} and Yoon, {Shin Hee} and Min, {Do Sik} and Jo, {Yang Hyeok} and Kim, {Myung Suk}",

note = "Funding Information: We thank Dr. Kaczmarek (Yale University School of Medicine, USA) for the Kv1.3 transfected CHO cells and Won Kim for reading the manuscript. This work was supported by the Catholic Medical Center Research Fund for Special Projects (1997). ",

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T1 - Inhibition of Kv1.3 channels by H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide) independent of protein kinase A

AU - Choi, Jin Sung

AU - Choi, Bok Hee

AU - Hahn, Sang June

AU - Yoon, Shin Hee

AU - Min, Do Sik

AU - Jo, Yang Hyeok

AU - Kim, Myung Suk

N1 - Funding Information: We thank Dr. Kaczmarek (Yale University School of Medicine, USA) for the Kv1.3 transfected CHO cells and Won Kim for reading the manuscript. This work was supported by the Catholic Medical Center Research Fund for Special Projects (1997).

PY - 2001/4/15

Y1 - 2001/4/15

N2 - The effects of H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide), a potent and selective inhibitor of protein kinase A (PKA), were examined on Kv1.3 channels stably expressed in Chinese hamster ovary (CHO) cells using the patch clamp technique. In whole-cell recordings, H-89 decreased Kv1.3 currents and accelerated the decay rate of current inactivation in a concentration-dependent manner with an ic50 value of 1.70 μM. These effects were completely reversible after washout. Intracellular infusion with PKA inhibitors, adenosine 3′, 5′-cyclic phosphorothioate-Rp (Rp-cAMPS) or protein kinase A inhibitor 5-24 (PKI 5-24) had no effect on Kv1.3 currents and did not prevent the inhibitory action of H-89 on the current. H-89 applied to the cytoplasmic surface also inhibited Kv1.3 currents in excised inside-out patches. These findings suggest that H-89 inhibits Kv1.3 currents independently of PKA.

AB - The effects of H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide), a potent and selective inhibitor of protein kinase A (PKA), were examined on Kv1.3 channels stably expressed in Chinese hamster ovary (CHO) cells using the patch clamp technique. In whole-cell recordings, H-89 decreased Kv1.3 currents and accelerated the decay rate of current inactivation in a concentration-dependent manner with an ic50 value of 1.70 μM. These effects were completely reversible after washout. Intracellular infusion with PKA inhibitors, adenosine 3′, 5′-cyclic phosphorothioate-Rp (Rp-cAMPS) or protein kinase A inhibitor 5-24 (PKI 5-24) had no effect on Kv1.3 currents and did not prevent the inhibitory action of H-89 on the current. H-89 applied to the cytoplasmic surface also inhibited Kv1.3 currents in excised inside-out patches. These findings suggest that H-89 inhibits Kv1.3 currents independently of PKA.

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Inhibition of Kv1.3 channels by H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide) independent of protein kinase A

Abstract

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