Facilitation of sympathetic neurotransmission by phosphatidylinositol-4,5- bisphosphate-dependent regulation of KCNQ channels in rat mesenteric arteries

Yasuo Kansui, Kenichi Goto, Toshio Ohtsubo, Noboru Murakami, Kunihiko Ichishima, Kiyoshi Matsumura, Takanari Kitazono

研究成果: ジャーナルへの寄稿記事

3 引用 (Scopus)

抄録

Sympathetic nerves regulate vascular tone by releasing neurotransmitters into the vasculature. We previously demonstrated that bradykinin facilitates sympathetic neurotransmission in rat mesenteric arteries. Although little is known about the intracellular mechanism modulating this neurotransmission, recent cell line experiments have shown that the KCNQ channel, which is inhibited by the depletion of membrane phosphatidylinositol-4,5-bisphosphate (PIP 2), participates in the control of neurotransmission by bradykinin. In the present study, we examined the mechanism regulating neurotransmitter release from rat perivascular sympathetic nerves. Excitatory junction potentials (EJPs) elicited by repetitive nerve stimulation (1 Hz, 11 pulses, 20 s, 20-50 V), a measure of sympathetic purinergic neurotransmission, were recorded with a conventional microelectrode technique in rat mesenteric arteries. Bradykinin (10 7 mol l 1) significantly enhanced the amplitude of EJPs (n22, P0.05). This enhancing effect was abolished by N-type calcium-channel inhibition with-conotoxin GVIA (2 × 10 9 mol l 1, n8). The blockade of phospholipase C with U-73122 (10 6 mol l 1, n17) also eliminated the facilitatory effect of bradykinin. In addition, the effects of bradykinin were diminished by the prevention of PIP 2 resynthesis with wortmannin (10 5 mol l 1 n7) or KCNQ channel inhibition with XE-991 (10 5 mol l 1, n7). On the other hand, depletion of intracellular calcium stores with cyclopiazonic acid (3 × 10 6 mol l 1, n6) or the inhibition of protein kinase C with bisindolylmaleimide-I (10 6 mol l 1, n9) did not alter the action of bradykinin. These data demonstrate that the hydrolysis of PIP 2 by phospholipase C, which is activated by G q/11-coupled receptors, and subsequent KCNQ channel inhibition enhance sympathetic purinergic neurotransmission presumably via the activation of N-type calcium channels in rat mesenteric arteries.

元の言語英語
ページ(範囲)909-916
ページ数8
ジャーナルHypertension Research
35
発行部数9
DOI
出版物ステータス出版済み - 9 1 2012

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Mesenteric Arteries
Bradykinin
Phosphatidylinositols
Synaptic Transmission
N-Type Calcium Channels
Type C Phospholipases
Neurotransmitter Agents
Conotoxins
Microelectrodes
Protein Kinase C
Blood Vessels
Hydrolysis
Calcium
Cell Line
Membranes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

これを引用

Facilitation of sympathetic neurotransmission by phosphatidylinositol-4,5- bisphosphate-dependent regulation of KCNQ channels in rat mesenteric arteries. / Kansui, Yasuo; Goto, Kenichi; Ohtsubo, Toshio; Murakami, Noboru; Ichishima, Kunihiko; Matsumura, Kiyoshi; Kitazono, Takanari.

:: Hypertension Research, 巻 35, 番号 9, 01.09.2012, p. 909-916.

研究成果: ジャーナルへの寄稿記事

Kansui, Yasuo ; Goto, Kenichi ; Ohtsubo, Toshio ; Murakami, Noboru ; Ichishima, Kunihiko ; Matsumura, Kiyoshi ; Kitazono, Takanari. / Facilitation of sympathetic neurotransmission by phosphatidylinositol-4,5- bisphosphate-dependent regulation of KCNQ channels in rat mesenteric arteries. :: Hypertension Research. 2012 ; 巻 35, 番号 9. pp. 909-916.
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abstract = "Sympathetic nerves regulate vascular tone by releasing neurotransmitters into the vasculature. We previously demonstrated that bradykinin facilitates sympathetic neurotransmission in rat mesenteric arteries. Although little is known about the intracellular mechanism modulating this neurotransmission, recent cell line experiments have shown that the KCNQ channel, which is inhibited by the depletion of membrane phosphatidylinositol-4,5-bisphosphate (PIP 2), participates in the control of neurotransmission by bradykinin. In the present study, we examined the mechanism regulating neurotransmitter release from rat perivascular sympathetic nerves. Excitatory junction potentials (EJPs) elicited by repetitive nerve stimulation (1 Hz, 11 pulses, 20 s, 20-50 V), a measure of sympathetic purinergic neurotransmission, were recorded with a conventional microelectrode technique in rat mesenteric arteries. Bradykinin (10 7 mol l 1) significantly enhanced the amplitude of EJPs (n22, P0.05). This enhancing effect was abolished by N-type calcium-channel inhibition with-conotoxin GVIA (2 × 10 9 mol l 1, n8). The blockade of phospholipase C with U-73122 (10 6 mol l 1, n17) also eliminated the facilitatory effect of bradykinin. In addition, the effects of bradykinin were diminished by the prevention of PIP 2 resynthesis with wortmannin (10 5 mol l 1 n7) or KCNQ channel inhibition with XE-991 (10 5 mol l 1, n7). On the other hand, depletion of intracellular calcium stores with cyclopiazonic acid (3 × 10 6 mol l 1, n6) or the inhibition of protein kinase C with bisindolylmaleimide-I (10 6 mol l 1, n9) did not alter the action of bradykinin. These data demonstrate that the hydrolysis of PIP 2 by phospholipase C, which is activated by G q/11-coupled receptors, and subsequent KCNQ channel inhibition enhance sympathetic purinergic neurotransmission presumably via the activation of N-type calcium channels in rat mesenteric arteries.",
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AU - Kansui, Yasuo

AU - Goto, Kenichi

AU - Ohtsubo, Toshio

AU - Murakami, Noboru

AU - Ichishima, Kunihiko

AU - Matsumura, Kiyoshi

AU - Kitazono, Takanari

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N2 - Sympathetic nerves regulate vascular tone by releasing neurotransmitters into the vasculature. We previously demonstrated that bradykinin facilitates sympathetic neurotransmission in rat mesenteric arteries. Although little is known about the intracellular mechanism modulating this neurotransmission, recent cell line experiments have shown that the KCNQ channel, which is inhibited by the depletion of membrane phosphatidylinositol-4,5-bisphosphate (PIP 2), participates in the control of neurotransmission by bradykinin. In the present study, we examined the mechanism regulating neurotransmitter release from rat perivascular sympathetic nerves. Excitatory junction potentials (EJPs) elicited by repetitive nerve stimulation (1 Hz, 11 pulses, 20 s, 20-50 V), a measure of sympathetic purinergic neurotransmission, were recorded with a conventional microelectrode technique in rat mesenteric arteries. Bradykinin (10 7 mol l 1) significantly enhanced the amplitude of EJPs (n22, P0.05). This enhancing effect was abolished by N-type calcium-channel inhibition with-conotoxin GVIA (2 × 10 9 mol l 1, n8). The blockade of phospholipase C with U-73122 (10 6 mol l 1, n17) also eliminated the facilitatory effect of bradykinin. In addition, the effects of bradykinin were diminished by the prevention of PIP 2 resynthesis with wortmannin (10 5 mol l 1 n7) or KCNQ channel inhibition with XE-991 (10 5 mol l 1, n7). On the other hand, depletion of intracellular calcium stores with cyclopiazonic acid (3 × 10 6 mol l 1, n6) or the inhibition of protein kinase C with bisindolylmaleimide-I (10 6 mol l 1, n9) did not alter the action of bradykinin. These data demonstrate that the hydrolysis of PIP 2 by phospholipase C, which is activated by G q/11-coupled receptors, and subsequent KCNQ channel inhibition enhance sympathetic purinergic neurotransmission presumably via the activation of N-type calcium channels in rat mesenteric arteries.

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