A novel carbamoyloxy arylalkanoyl arylpiperazine compound (SKL-NP) inhibits hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents in rat dorsal root ganglion neurons

Gehoon Chung; Tae Hyung Kim; Hyewon Shin; Eunhee Chae; Hanju Yi; Hongsik Moon; Hyun Jin Kim; Joong Soo Kim; Sung Jun Jung; Seog Bae Oh

doi:10.4196/kjpp.2012.16.4.237

A novel carbamoyloxy arylalkanoyl arylpiperazine compound (SKL-NP) inhibits hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents in rat dorsal root ganglion neurons

Gehoon Chung
, Tae Hyung Kim
, Hyewon Shin
, Eunhee Chae
, Hanju Yi
, Hongsik Moon
, Hyun Jin Kim
, Joong Soo Kim
, Sung Jun Jung
, Seog Bae Oh

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

1 Scopus citations

Abstract

In this study, we determined mode of action of a novel carbamoyloxy arylalkanoyl arylpiperazine compound (SKL-NP) on hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents (Z _h) that plays important roles in neuropathic pain. In small or medium-sized dorsal root ganglion (DRG) neurons (<40 μm in diameter) exhibiting tonic firing and prominent I _h, SKL-NP inhibited I _h and spike firings in a concentration dependent manner (IC ₅₀=7.85 μM). SKL-NP-induced inhibition of I _h was blocked by pretreatment of pertussis toxin (PTX) and N-ethylmaleimide (NEM) as well as 8-Br-cAMP, a membrane permeable cAMP analogue. These results suggest that SKL-NP modulates I _h in indirect manner by the activation of a Gi-protein coupled receptor that decreases intracellular cAMP concentration. Taken together, SKL-NP has the inhibitory effect on HCN channel currents (I _h) in DRG neurons of rats.

Original language	English
Pages (from-to)	237-241
Number of pages	5
Journal	Korean Journal of Physiology and Pharmacology
Volume	16
Issue number	4
DOIs	https://doi.org/10.4196/kjpp.2012.16.4.237
State	Published - Aug 2012
Externally published	Yes

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

cAMP
G -protein
Hyperpolarization-activated cyclic nucleotide-gated channel
I
Neuropathic pain

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10.4196/kjpp.2012.16.4.237

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Chung, G., Kim, T. H., Shin, H., Chae, E., Yi, H., Moon, H., Kim, H. J., Kim, J. S., Jung, S. J., & Oh, S. B. (2012). A novel carbamoyloxy arylalkanoyl arylpiperazine compound (SKL-NP) inhibits hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents in rat dorsal root ganglion neurons. Korean Journal of Physiology and Pharmacology, 16(4), 237-241. https://doi.org/10.4196/kjpp.2012.16.4.237

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title = "A novel carbamoyloxy arylalkanoyl arylpiperazine compound (SKL-NP) inhibits hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents in rat dorsal root ganglion neurons",

abstract = "In this study, we determined mode of action of a novel carbamoyloxy arylalkanoyl arylpiperazine compound (SKL-NP) on hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents (Z h) that plays important roles in neuropathic pain. In small or medium-sized dorsal root ganglion (DRG) neurons (<40 μm in diameter) exhibiting tonic firing and prominent I h, SKL-NP inhibited I h and spike firings in a concentration dependent manner (IC 50=7.85 μM). SKL-NP-induced inhibition of I h was blocked by pretreatment of pertussis toxin (PTX) and N-ethylmaleimide (NEM) as well as 8-Br-cAMP, a membrane permeable cAMP analogue. These results suggest that SKL-NP modulates I h in indirect manner by the activation of a Gi-protein coupled receptor that decreases intracellular cAMP concentration. Taken together, SKL-NP has the inhibitory effect on HCN channel currents (I h) in DRG neurons of rats.",

keywords = "cAMP, G -protein, Hyperpolarization-activated cyclic nucleotide-gated channel, I, Neuropathic pain",

author = "Gehoon Chung and Kim, \{Tae Hyung\} and Hyewon Shin and Eunhee Chae and Hanju Yi and Hongsik Moon and Kim, \{Hyun Jin\} and Kim, \{Joong Soo\} and Jung, \{Sung Jun\} and Oh, \{Seog Bae\}",

year = "2012",

month = aug,

doi = "10.4196/kjpp.2012.16.4.237",

language = "English",

volume = "16",

pages = "237--241",

journal = "Korean Journal of Physiology and Pharmacology",

issn = "1226-4512",

publisher = "Korean Physiological Soc. and Korean Soc. of Pharmacology",

number = "4",

}

Chung, G, Kim, TH, Shin, H, Chae, E, Yi, H, Moon, H, Kim, HJ, Kim, JS, Jung, SJ & Oh, SB 2012, 'A novel carbamoyloxy arylalkanoyl arylpiperazine compound (SKL-NP) inhibits hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents in rat dorsal root ganglion neurons', Korean Journal of Physiology and Pharmacology, vol. 16, no. 4, pp. 237-241. https://doi.org/10.4196/kjpp.2012.16.4.237

A novel carbamoyloxy arylalkanoyl arylpiperazine compound (SKL-NP) inhibits hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents in rat dorsal root ganglion neurons. / Chung, Gehoon; Kim, Tae Hyung; Shin, Hyewon et al.
In: Korean Journal of Physiology and Pharmacology, Vol. 16, No. 4, 08.2012, p. 237-241.

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

TY - JOUR

T1 - A novel carbamoyloxy arylalkanoyl arylpiperazine compound (SKL-NP) inhibits hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents in rat dorsal root ganglion neurons

AU - Chung, Gehoon

AU - Kim, Tae Hyung

AU - Shin, Hyewon

AU - Chae, Eunhee

AU - Yi, Hanju

AU - Moon, Hongsik

AU - Kim, Hyun Jin

AU - Kim, Joong Soo

AU - Jung, Sung Jun

AU - Oh, Seog Bae

PY - 2012/8

Y1 - 2012/8

N2 - In this study, we determined mode of action of a novel carbamoyloxy arylalkanoyl arylpiperazine compound (SKL-NP) on hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents (Z h) that plays important roles in neuropathic pain. In small or medium-sized dorsal root ganglion (DRG) neurons (<40 μm in diameter) exhibiting tonic firing and prominent I h, SKL-NP inhibited I h and spike firings in a concentration dependent manner (IC 50=7.85 μM). SKL-NP-induced inhibition of I h was blocked by pretreatment of pertussis toxin (PTX) and N-ethylmaleimide (NEM) as well as 8-Br-cAMP, a membrane permeable cAMP analogue. These results suggest that SKL-NP modulates I h in indirect manner by the activation of a Gi-protein coupled receptor that decreases intracellular cAMP concentration. Taken together, SKL-NP has the inhibitory effect on HCN channel currents (I h) in DRG neurons of rats.

AB - In this study, we determined mode of action of a novel carbamoyloxy arylalkanoyl arylpiperazine compound (SKL-NP) on hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents (Z h) that plays important roles in neuropathic pain. In small or medium-sized dorsal root ganglion (DRG) neurons (<40 μm in diameter) exhibiting tonic firing and prominent I h, SKL-NP inhibited I h and spike firings in a concentration dependent manner (IC 50=7.85 μM). SKL-NP-induced inhibition of I h was blocked by pretreatment of pertussis toxin (PTX) and N-ethylmaleimide (NEM) as well as 8-Br-cAMP, a membrane permeable cAMP analogue. These results suggest that SKL-NP modulates I h in indirect manner by the activation of a Gi-protein coupled receptor that decreases intracellular cAMP concentration. Taken together, SKL-NP has the inhibitory effect on HCN channel currents (I h) in DRG neurons of rats.

KW - cAMP

KW - G -protein

KW - Hyperpolarization-activated cyclic nucleotide-gated channel

KW - I

KW - Neuropathic pain

UR - https://www.scopus.com/pages/publications/84865808004

U2 - 10.4196/kjpp.2012.16.4.237

DO - 10.4196/kjpp.2012.16.4.237

M3 - Article

AN - SCOPUS:84865808004

SN - 1226-4512

VL - 16

SP - 237

EP - 241

JO - Korean Journal of Physiology and Pharmacology

JF - Korean Journal of Physiology and Pharmacology

IS - 4

ER -

A novel carbamoyloxy arylalkanoyl arylpiperazine compound (SKL-NP) inhibits hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents in rat dorsal root ganglion neurons

Abstract

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