Role of TRPV1 and intracellular Ca2+ in excitation of cardiac sensory neurons by bradykinin

Zizhen Wu, Hui Lin Pan

Research output: Contribution to journalArticle

Abstract

Bradykinin is an important mediator produced during myocardial ischemia and infarction that can activate and/or sensitize cardiac spinal (sympathetic) sensory neurons to trigger chest pain. Because a long-onset latency is associated with the bradykinin effect on cardiac spinal afferents, a cascade of intracellular signaling events is likely involved in the action of bradykinin on cardiac nociceptors. In this study, we determined the signal transduction mechanisms involved in bradykinin stimulation of cardiac nociceptors. Cardiac dorsal root ganglion (DRG) neurons in rats were labeled by intracardiac injection of a fluorescent tracer, 1,1′-dioctadecyl-3,3,3′,3′- tetramethylindocarbocyanine percholate (DiI). Whole cell current-clamp recordings were performed in acutely isolated DRG neurons. In DiI-labeled DRG neurons, 1 μM bradykinin significantly increased the firing frequency and lowered the membrane potential. Iodoresiniferatoxin, a highly specific transient receptor potential vanilloid type 1 (TRPV1) antagonist, significantly reduced the excitatory effect of bradykinin. Furthermore, the stimulating effect of bradykinin on DiI-labeled DRG neurons was significantly attenuated by baicalein (a selective inhibitor of 12-lipoxygenase) or 2-aminoethyl diphenylborinate [an inositol 1,4,5-trisphosphate (IP3) antagonist]. In addition, the effect of bradykinin on cardiac DRG neurons was abolished after the neurons were treated with BAPTA-AM or thapsigargin (to deplete intracellular Ca2+ stores) but not in the Ca2+-free extracellular solution. Collectively, these findings provide new evidence that 12-lipoxygenase products, IP3, and TRPV1 channels contribute importantly to excitation of cardiac nociceptors by bradykinin. Activation of TRPV1 and the increase in the intracellular Ca2+ are critically involved in activation/ sensitization of cardiac nociceptors by bradykinin.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume293
Issue number1
DOIs
StatePublished - Jul 1 2007
Externally publishedYes

Fingerprint

Bradykinin
Sensory Receptor Cells
Spinal Ganglia
Nociceptors
Neurons
vanilloid receptor subtype 1
Arachidonate 12-Lipoxygenase
Inositol 1,4,5-Trisphosphate Receptors
Inositol 1,4,5-Trisphosphate
Thapsigargin
Lipoxygenase
Chest Pain
Membrane Potentials
Myocardial Ischemia
Signal Transduction
Myocardial Infarction
Injections

Keywords

  • Cardiac afferents
  • Dorsal root ganglia
  • Transient receptor potential vanilloid type 1

ASJC Scopus subject areas

  • Physiology

Cite this

@article{ba0c72d841874451944c2e200b72b5c0,
title = "Role of TRPV1 and intracellular Ca2+ in excitation of cardiac sensory neurons by bradykinin",
abstract = "Bradykinin is an important mediator produced during myocardial ischemia and infarction that can activate and/or sensitize cardiac spinal (sympathetic) sensory neurons to trigger chest pain. Because a long-onset latency is associated with the bradykinin effect on cardiac spinal afferents, a cascade of intracellular signaling events is likely involved in the action of bradykinin on cardiac nociceptors. In this study, we determined the signal transduction mechanisms involved in bradykinin stimulation of cardiac nociceptors. Cardiac dorsal root ganglion (DRG) neurons in rats were labeled by intracardiac injection of a fluorescent tracer, 1,1′-dioctadecyl-3,3,3′,3′- tetramethylindocarbocyanine percholate (DiI). Whole cell current-clamp recordings were performed in acutely isolated DRG neurons. In DiI-labeled DRG neurons, 1 μM bradykinin significantly increased the firing frequency and lowered the membrane potential. Iodoresiniferatoxin, a highly specific transient receptor potential vanilloid type 1 (TRPV1) antagonist, significantly reduced the excitatory effect of bradykinin. Furthermore, the stimulating effect of bradykinin on DiI-labeled DRG neurons was significantly attenuated by baicalein (a selective inhibitor of 12-lipoxygenase) or 2-aminoethyl diphenylborinate [an inositol 1,4,5-trisphosphate (IP3) antagonist]. In addition, the effect of bradykinin on cardiac DRG neurons was abolished after the neurons were treated with BAPTA-AM or thapsigargin (to deplete intracellular Ca2+ stores) but not in the Ca2+-free extracellular solution. Collectively, these findings provide new evidence that 12-lipoxygenase products, IP3, and TRPV1 channels contribute importantly to excitation of cardiac nociceptors by bradykinin. Activation of TRPV1 and the increase in the intracellular Ca2+ are critically involved in activation/ sensitization of cardiac nociceptors by bradykinin.",
keywords = "Cardiac afferents, Dorsal root ganglia, Transient receptor potential vanilloid type 1",
author = "Zizhen Wu and Pan, {Hui Lin}",
year = "2007",
month = "7",
day = "1",
doi = "10.1152/ajpregu.00094.2007",
language = "English (US)",
volume = "293",
journal = "American Journal of Physiology",
issn = "0363-6119",
publisher = "American Physiological Society",
number = "1",

}

TY - JOUR

T1 - Role of TRPV1 and intracellular Ca2+ in excitation of cardiac sensory neurons by bradykinin

AU - Wu, Zizhen

AU - Pan, Hui Lin

PY - 2007/7/1

Y1 - 2007/7/1

N2 - Bradykinin is an important mediator produced during myocardial ischemia and infarction that can activate and/or sensitize cardiac spinal (sympathetic) sensory neurons to trigger chest pain. Because a long-onset latency is associated with the bradykinin effect on cardiac spinal afferents, a cascade of intracellular signaling events is likely involved in the action of bradykinin on cardiac nociceptors. In this study, we determined the signal transduction mechanisms involved in bradykinin stimulation of cardiac nociceptors. Cardiac dorsal root ganglion (DRG) neurons in rats were labeled by intracardiac injection of a fluorescent tracer, 1,1′-dioctadecyl-3,3,3′,3′- tetramethylindocarbocyanine percholate (DiI). Whole cell current-clamp recordings were performed in acutely isolated DRG neurons. In DiI-labeled DRG neurons, 1 μM bradykinin significantly increased the firing frequency and lowered the membrane potential. Iodoresiniferatoxin, a highly specific transient receptor potential vanilloid type 1 (TRPV1) antagonist, significantly reduced the excitatory effect of bradykinin. Furthermore, the stimulating effect of bradykinin on DiI-labeled DRG neurons was significantly attenuated by baicalein (a selective inhibitor of 12-lipoxygenase) or 2-aminoethyl diphenylborinate [an inositol 1,4,5-trisphosphate (IP3) antagonist]. In addition, the effect of bradykinin on cardiac DRG neurons was abolished after the neurons were treated with BAPTA-AM or thapsigargin (to deplete intracellular Ca2+ stores) but not in the Ca2+-free extracellular solution. Collectively, these findings provide new evidence that 12-lipoxygenase products, IP3, and TRPV1 channels contribute importantly to excitation of cardiac nociceptors by bradykinin. Activation of TRPV1 and the increase in the intracellular Ca2+ are critically involved in activation/ sensitization of cardiac nociceptors by bradykinin.

AB - Bradykinin is an important mediator produced during myocardial ischemia and infarction that can activate and/or sensitize cardiac spinal (sympathetic) sensory neurons to trigger chest pain. Because a long-onset latency is associated with the bradykinin effect on cardiac spinal afferents, a cascade of intracellular signaling events is likely involved in the action of bradykinin on cardiac nociceptors. In this study, we determined the signal transduction mechanisms involved in bradykinin stimulation of cardiac nociceptors. Cardiac dorsal root ganglion (DRG) neurons in rats were labeled by intracardiac injection of a fluorescent tracer, 1,1′-dioctadecyl-3,3,3′,3′- tetramethylindocarbocyanine percholate (DiI). Whole cell current-clamp recordings were performed in acutely isolated DRG neurons. In DiI-labeled DRG neurons, 1 μM bradykinin significantly increased the firing frequency and lowered the membrane potential. Iodoresiniferatoxin, a highly specific transient receptor potential vanilloid type 1 (TRPV1) antagonist, significantly reduced the excitatory effect of bradykinin. Furthermore, the stimulating effect of bradykinin on DiI-labeled DRG neurons was significantly attenuated by baicalein (a selective inhibitor of 12-lipoxygenase) or 2-aminoethyl diphenylborinate [an inositol 1,4,5-trisphosphate (IP3) antagonist]. In addition, the effect of bradykinin on cardiac DRG neurons was abolished after the neurons were treated with BAPTA-AM or thapsigargin (to deplete intracellular Ca2+ stores) but not in the Ca2+-free extracellular solution. Collectively, these findings provide new evidence that 12-lipoxygenase products, IP3, and TRPV1 channels contribute importantly to excitation of cardiac nociceptors by bradykinin. Activation of TRPV1 and the increase in the intracellular Ca2+ are critically involved in activation/ sensitization of cardiac nociceptors by bradykinin.

KW - Cardiac afferents

KW - Dorsal root ganglia

KW - Transient receptor potential vanilloid type 1

UR - http://www.scopus.com/inward/record.url?scp=34447628818&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34447628818&partnerID=8YFLogxK

U2 - 10.1152/ajpregu.00094.2007

DO - 10.1152/ajpregu.00094.2007

M3 - Article

C2 - 17491115

AN - SCOPUS:34447628818

VL - 293

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6119

IS - 1

ER -