Low-level vagus nerve stimulation upregulates small conductance calcium-activated potassium channels in the stellate ganglion

Mark J. Shen, Hao Che Chang, Hyung Wook Park, A. George Akingba, Po Cheng Chang, Zheng Zhang, Shien Fong Lin, Changyu Shen, Lan S. Chen, Zhenhui Chen, Michael C. Fishbein, Nipavan Chiamvimonvat, Peng Sheng Chen

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

BACKGROUND Small conductance calcium-activated potassium (SK) channels are responsible for afterhyperpolarization that suppresses nerve discharges. OBJECTIVES To test the hypothesis that low-level vagus nerve stimulation (LL-VNS) leads to the upregulation of SK2 proteins in the left stellate ganglion. METHODS Six dogs (group 1) underwent 1-week LL-VNS of the left cervical vagus nerve. Five normal dogs (group 2) were used as controls. SK2 protein levels were examined by using Western blotting. The ratio between SK2 and glyceraldehydes-3-phosphate-dehydrogenase levels was used as an arbitrary unit (AU). RESULTS We found higher SK2 expression in group 1 (0.124 ± 0.049 AU) than in group 2 (0.085 ± 0.031 AU; P < .05). Immunostaining showed that the density of nerve structures stained with SK2 antibody was also higher in group 1 (11,546 ± 7,271 μm2/mm2) than in group 2 (5321 ± 3164 μm2/ mm2; P < .05). There were significantly more ganglion cells without immunoreactivity to tyrosine hydroxylase (TH) in group 1 (11.4% ± 2.3%) than in group 2 (4.9% ± 0.7%; P < .05). The TH-negative ganglion cells mostly stained positive for choline acetyltransferase (95.9% ± 2.8% in group 1 and 86.1% ± 4.4% in group 2; P = .10). Immunofluorescence confocal microscopy revealed a significant decrease in the SK2 staining in the cytosol but an increase in the SK2 staining on the membrane of the ganglion cells in group 1 compared to group 2. CONCLUSIONS Left LL-VNS results in the upregulation of SK2 proteins, increased SK2 protein expression in the cell membrane, and increased TH-negative (mostly choline acetyltransferase-pos-itive) ganglion cells in the left stellate ganglion. These changes may underlie the antiarrhythmic efficacy of LL-VNS in ambulatory dogs.

Original languageEnglish (US)
Pages (from-to)910-915
Number of pages6
JournalHeart Rhythm
Volume10
Issue number6
DOIs
StatePublished - Jun 2013

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Small-Conductance Calcium-Activated Potassium Channels
Stellate Ganglion
Vagus Nerve Stimulation
Ganglia
Tyrosine 3-Monooxygenase
Up-Regulation
Choline O-Acetyltransferase
Dogs
Proteins
Cell Membrane
Staining and Labeling
Glyceraldehyde-3-Phosphate Dehydrogenases
Vagus Nerve
Fluorescence Microscopy
Confocal Microscopy
Cytosol
Western Blotting
Antibodies

Keywords

  • Autonomic nervous system
  • Small conductance calcium-activated potassium channel
  • Stellate ganglion
  • Vagus nerve stimulation
  • Western blot

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Shen, M. J., Chang, H. C., Park, H. W., Akingba, A. G., Chang, P. C., Zhang, Z., ... Chen, P. S. (2013). Low-level vagus nerve stimulation upregulates small conductance calcium-activated potassium channels in the stellate ganglion. Heart Rhythm, 10(6), 910-915. https://doi.org/10.1016/j.hrthm.2013.01.029

Low-level vagus nerve stimulation upregulates small conductance calcium-activated potassium channels in the stellate ganglion. / Shen, Mark J.; Chang, Hao Che; Park, Hyung Wook; Akingba, A. George; Chang, Po Cheng; Zhang, Zheng; Lin, Shien Fong; Shen, Changyu; Chen, Lan S.; Chen, Zhenhui; Fishbein, Michael C.; Chiamvimonvat, Nipavan; Chen, Peng Sheng.

In: Heart Rhythm, Vol. 10, No. 6, 06.2013, p. 910-915.

Research output: Contribution to journalArticle

Shen, MJ, Chang, HC, Park, HW, Akingba, AG, Chang, PC, Zhang, Z, Lin, SF, Shen, C, Chen, LS, Chen, Z, Fishbein, MC, Chiamvimonvat, N & Chen, PS 2013, 'Low-level vagus nerve stimulation upregulates small conductance calcium-activated potassium channels in the stellate ganglion', Heart Rhythm, vol. 10, no. 6, pp. 910-915. https://doi.org/10.1016/j.hrthm.2013.01.029
Shen, Mark J. ; Chang, Hao Che ; Park, Hyung Wook ; Akingba, A. George ; Chang, Po Cheng ; Zhang, Zheng ; Lin, Shien Fong ; Shen, Changyu ; Chen, Lan S. ; Chen, Zhenhui ; Fishbein, Michael C. ; Chiamvimonvat, Nipavan ; Chen, Peng Sheng. / Low-level vagus nerve stimulation upregulates small conductance calcium-activated potassium channels in the stellate ganglion. In: Heart Rhythm. 2013 ; Vol. 10, No. 6. pp. 910-915.
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abstract = "BACKGROUND Small conductance calcium-activated potassium (SK) channels are responsible for afterhyperpolarization that suppresses nerve discharges. OBJECTIVES To test the hypothesis that low-level vagus nerve stimulation (LL-VNS) leads to the upregulation of SK2 proteins in the left stellate ganglion. METHODS Six dogs (group 1) underwent 1-week LL-VNS of the left cervical vagus nerve. Five normal dogs (group 2) were used as controls. SK2 protein levels were examined by using Western blotting. The ratio between SK2 and glyceraldehydes-3-phosphate-dehydrogenase levels was used as an arbitrary unit (AU). RESULTS We found higher SK2 expression in group 1 (0.124 ± 0.049 AU) than in group 2 (0.085 ± 0.031 AU; P < .05). Immunostaining showed that the density of nerve structures stained with SK2 antibody was also higher in group 1 (11,546 ± 7,271 μm2/mm2) than in group 2 (5321 ± 3164 μm2/ mm2; P < .05). There were significantly more ganglion cells without immunoreactivity to tyrosine hydroxylase (TH) in group 1 (11.4{\%} ± 2.3{\%}) than in group 2 (4.9{\%} ± 0.7{\%}; P < .05). The TH-negative ganglion cells mostly stained positive for choline acetyltransferase (95.9{\%} ± 2.8{\%} in group 1 and 86.1{\%} ± 4.4{\%} in group 2; P = .10). Immunofluorescence confocal microscopy revealed a significant decrease in the SK2 staining in the cytosol but an increase in the SK2 staining on the membrane of the ganglion cells in group 1 compared to group 2. CONCLUSIONS Left LL-VNS results in the upregulation of SK2 proteins, increased SK2 protein expression in the cell membrane, and increased TH-negative (mostly choline acetyltransferase-pos-itive) ganglion cells in the left stellate ganglion. These changes may underlie the antiarrhythmic efficacy of LL-VNS in ambulatory dogs.",
keywords = "Autonomic nervous system, Small conductance calcium-activated potassium channel, Stellate ganglion, Vagus nerve stimulation, Western blot",
author = "Shen, {Mark J.} and Chang, {Hao Che} and Park, {Hyung Wook} and Akingba, {A. George} and Chang, {Po Cheng} and Zheng Zhang and Lin, {Shien Fong} and Changyu Shen and Chen, {Lan S.} and Zhenhui Chen and Fishbein, {Michael C.} and Nipavan Chiamvimonvat and Chen, {Peng Sheng}",
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T1 - Low-level vagus nerve stimulation upregulates small conductance calcium-activated potassium channels in the stellate ganglion

AU - Shen, Mark J.

AU - Chang, Hao Che

AU - Park, Hyung Wook

AU - Akingba, A. George

AU - Chang, Po Cheng

AU - Zhang, Zheng

AU - Lin, Shien Fong

AU - Shen, Changyu

AU - Chen, Lan S.

AU - Chen, Zhenhui

AU - Fishbein, Michael C.

AU - Chiamvimonvat, Nipavan

AU - Chen, Peng Sheng

PY - 2013/6

Y1 - 2013/6

N2 - BACKGROUND Small conductance calcium-activated potassium (SK) channels are responsible for afterhyperpolarization that suppresses nerve discharges. OBJECTIVES To test the hypothesis that low-level vagus nerve stimulation (LL-VNS) leads to the upregulation of SK2 proteins in the left stellate ganglion. METHODS Six dogs (group 1) underwent 1-week LL-VNS of the left cervical vagus nerve. Five normal dogs (group 2) were used as controls. SK2 protein levels were examined by using Western blotting. The ratio between SK2 and glyceraldehydes-3-phosphate-dehydrogenase levels was used as an arbitrary unit (AU). RESULTS We found higher SK2 expression in group 1 (0.124 ± 0.049 AU) than in group 2 (0.085 ± 0.031 AU; P < .05). Immunostaining showed that the density of nerve structures stained with SK2 antibody was also higher in group 1 (11,546 ± 7,271 μm2/mm2) than in group 2 (5321 ± 3164 μm2/ mm2; P < .05). There were significantly more ganglion cells without immunoreactivity to tyrosine hydroxylase (TH) in group 1 (11.4% ± 2.3%) than in group 2 (4.9% ± 0.7%; P < .05). The TH-negative ganglion cells mostly stained positive for choline acetyltransferase (95.9% ± 2.8% in group 1 and 86.1% ± 4.4% in group 2; P = .10). Immunofluorescence confocal microscopy revealed a significant decrease in the SK2 staining in the cytosol but an increase in the SK2 staining on the membrane of the ganglion cells in group 1 compared to group 2. CONCLUSIONS Left LL-VNS results in the upregulation of SK2 proteins, increased SK2 protein expression in the cell membrane, and increased TH-negative (mostly choline acetyltransferase-pos-itive) ganglion cells in the left stellate ganglion. These changes may underlie the antiarrhythmic efficacy of LL-VNS in ambulatory dogs.

AB - BACKGROUND Small conductance calcium-activated potassium (SK) channels are responsible for afterhyperpolarization that suppresses nerve discharges. OBJECTIVES To test the hypothesis that low-level vagus nerve stimulation (LL-VNS) leads to the upregulation of SK2 proteins in the left stellate ganglion. METHODS Six dogs (group 1) underwent 1-week LL-VNS of the left cervical vagus nerve. Five normal dogs (group 2) were used as controls. SK2 protein levels were examined by using Western blotting. The ratio between SK2 and glyceraldehydes-3-phosphate-dehydrogenase levels was used as an arbitrary unit (AU). RESULTS We found higher SK2 expression in group 1 (0.124 ± 0.049 AU) than in group 2 (0.085 ± 0.031 AU; P < .05). Immunostaining showed that the density of nerve structures stained with SK2 antibody was also higher in group 1 (11,546 ± 7,271 μm2/mm2) than in group 2 (5321 ± 3164 μm2/ mm2; P < .05). There were significantly more ganglion cells without immunoreactivity to tyrosine hydroxylase (TH) in group 1 (11.4% ± 2.3%) than in group 2 (4.9% ± 0.7%; P < .05). The TH-negative ganglion cells mostly stained positive for choline acetyltransferase (95.9% ± 2.8% in group 1 and 86.1% ± 4.4% in group 2; P = .10). Immunofluorescence confocal microscopy revealed a significant decrease in the SK2 staining in the cytosol but an increase in the SK2 staining on the membrane of the ganglion cells in group 1 compared to group 2. CONCLUSIONS Left LL-VNS results in the upregulation of SK2 proteins, increased SK2 protein expression in the cell membrane, and increased TH-negative (mostly choline acetyltransferase-pos-itive) ganglion cells in the left stellate ganglion. These changes may underlie the antiarrhythmic efficacy of LL-VNS in ambulatory dogs.

KW - Autonomic nervous system

KW - Small conductance calcium-activated potassium channel

KW - Stellate ganglion

KW - Vagus nerve stimulation

KW - Western blot

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