Expression profiles of high voltage-activated calcium channels in sympathetic and parasympathetic pelvic ganglion neurons innervating the urogenital system

Yu Jin Won, Kum Whang, Deok Kong In, Kyusang Park, Joong Woo Lee, Seong Woo Jeong

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Among the autonomic ganglia, major pelvic ganglia (MPG) innervating the urogenital system are unique because both sympathetic and parasympathetic neurons are colocalized within one ganglion capsule. Sympathetic MPG neurons are discriminated from parasympathetic ones by expression of low voltage-activated Ca2+ channels that primarily arise from T-type α1H isoform and contribute to the generation of low-threshold spikes. Until now, however, expression profiles of high voltage-activated (HVA) Ca2+ channels in these two populations of MPG neurons remain unknown. Thus, in the present study, we dissected out HVA Ca2+ channels using pharmacological and molecular biological tools. Reverse transcription-polymerase chain reaction analysis showed that MPG neurons contained transcripts encoding all of the known HVA Ca2+ channel isoforms (α1B, α1C, α1D, and α1E), with the exception of α1A. Western blot analysis and pharmacology with ω-agatoxin IVA (1 μM) confirmed that MPG neurons lack the α1A Ca2+ channels. Unexpectedly, the expression profile of HVA Ca2+ channel isoforms was identical in the sympathetic and parasympathetic neurons of the MPG. Of the total Ca2+ currents, ω-conotoxin GVIA-sensitive N-type (α1B) currents constituted 57 ± 5% (n = 9) and 60 ± 3% (n = 6), respectively; nimodipine-sensitive L-type (α1C and α1D) currents made up 17 ± 4% and 14 ± 2%, respectively; and nimodipine-resistant and ω-conotoxin GVIA-resistant R-type currents were 25 ± 3% and 22 ± 2%, respectively. The R-type Ca2+ currents were sensitive to NiCl2 (IC50 = 22 ± 0.1 μM) but not to SNX-482, which was able to potently (IC50 = 76 ± 0.4 nM) block the recombinant α1E2a/ α2δ Ca2+ currents expressed in human embryonic kidney 293 cells. Taken together, our data suggest that sympathetic and parasympathetic MPG neurons share a similar but unique profile of HVA Ca 2+ channel isoforms.

Original languageEnglish
Pages (from-to)1064-1071
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume317
Issue number3
DOIs
Publication statusPublished - 2006 Jun 1

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Parasympathetic Ganglia
Urogenital System
Calcium Channels
Ganglia
Neurons
Protein Isoforms
Conotoxins
Nimodipine
Inhibitory Concentration 50
Agatoxins
Autonomic Ganglia
Pharmacology
Reverse Transcription
Capsules
Western Blotting
Kidney
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

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title = "Expression profiles of high voltage-activated calcium channels in sympathetic and parasympathetic pelvic ganglion neurons innervating the urogenital system",
abstract = "Among the autonomic ganglia, major pelvic ganglia (MPG) innervating the urogenital system are unique because both sympathetic and parasympathetic neurons are colocalized within one ganglion capsule. Sympathetic MPG neurons are discriminated from parasympathetic ones by expression of low voltage-activated Ca2+ channels that primarily arise from T-type α1H isoform and contribute to the generation of low-threshold spikes. Until now, however, expression profiles of high voltage-activated (HVA) Ca2+ channels in these two populations of MPG neurons remain unknown. Thus, in the present study, we dissected out HVA Ca2+ channels using pharmacological and molecular biological tools. Reverse transcription-polymerase chain reaction analysis showed that MPG neurons contained transcripts encoding all of the known HVA Ca2+ channel isoforms (α1B, α1C, α1D, and α1E), with the exception of α1A. Western blot analysis and pharmacology with ω-agatoxin IVA (1 μM) confirmed that MPG neurons lack the α1A Ca2+ channels. Unexpectedly, the expression profile of HVA Ca2+ channel isoforms was identical in the sympathetic and parasympathetic neurons of the MPG. Of the total Ca2+ currents, ω-conotoxin GVIA-sensitive N-type (α1B) currents constituted 57 ± 5{\%} (n = 9) and 60 ± 3{\%} (n = 6), respectively; nimodipine-sensitive L-type (α1C and α1D) currents made up 17 ± 4{\%} and 14 ± 2{\%}, respectively; and nimodipine-resistant and ω-conotoxin GVIA-resistant R-type currents were 25 ± 3{\%} and 22 ± 2{\%}, respectively. The R-type Ca2+ currents were sensitive to NiCl2 (IC50 = 22 ± 0.1 μM) but not to SNX-482, which was able to potently (IC50 = 76 ± 0.4 nM) block the recombinant α1E/β2a/ α2δ Ca2+ currents expressed in human embryonic kidney 293 cells. Taken together, our data suggest that sympathetic and parasympathetic MPG neurons share a similar but unique profile of HVA Ca 2+ channel isoforms.",
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Expression profiles of high voltage-activated calcium channels in sympathetic and parasympathetic pelvic ganglion neurons innervating the urogenital system. / Won, Yu Jin; Whang, Kum; In, Deok Kong; Park, Kyusang; Lee, Joong Woo; Jeong, Seong Woo.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 317, No. 3, 01.06.2006, p. 1064-1071.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Expression profiles of high voltage-activated calcium channels in sympathetic and parasympathetic pelvic ganglion neurons innervating the urogenital system

AU - Won, Yu Jin

AU - Whang, Kum

AU - In, Deok Kong

AU - Park, Kyusang

AU - Lee, Joong Woo

AU - Jeong, Seong Woo

PY - 2006/6/1

Y1 - 2006/6/1

N2 - Among the autonomic ganglia, major pelvic ganglia (MPG) innervating the urogenital system are unique because both sympathetic and parasympathetic neurons are colocalized within one ganglion capsule. Sympathetic MPG neurons are discriminated from parasympathetic ones by expression of low voltage-activated Ca2+ channels that primarily arise from T-type α1H isoform and contribute to the generation of low-threshold spikes. Until now, however, expression profiles of high voltage-activated (HVA) Ca2+ channels in these two populations of MPG neurons remain unknown. Thus, in the present study, we dissected out HVA Ca2+ channels using pharmacological and molecular biological tools. Reverse transcription-polymerase chain reaction analysis showed that MPG neurons contained transcripts encoding all of the known HVA Ca2+ channel isoforms (α1B, α1C, α1D, and α1E), with the exception of α1A. Western blot analysis and pharmacology with ω-agatoxin IVA (1 μM) confirmed that MPG neurons lack the α1A Ca2+ channels. Unexpectedly, the expression profile of HVA Ca2+ channel isoforms was identical in the sympathetic and parasympathetic neurons of the MPG. Of the total Ca2+ currents, ω-conotoxin GVIA-sensitive N-type (α1B) currents constituted 57 ± 5% (n = 9) and 60 ± 3% (n = 6), respectively; nimodipine-sensitive L-type (α1C and α1D) currents made up 17 ± 4% and 14 ± 2%, respectively; and nimodipine-resistant and ω-conotoxin GVIA-resistant R-type currents were 25 ± 3% and 22 ± 2%, respectively. The R-type Ca2+ currents were sensitive to NiCl2 (IC50 = 22 ± 0.1 μM) but not to SNX-482, which was able to potently (IC50 = 76 ± 0.4 nM) block the recombinant α1E/β2a/ α2δ Ca2+ currents expressed in human embryonic kidney 293 cells. Taken together, our data suggest that sympathetic and parasympathetic MPG neurons share a similar but unique profile of HVA Ca 2+ channel isoforms.

AB - Among the autonomic ganglia, major pelvic ganglia (MPG) innervating the urogenital system are unique because both sympathetic and parasympathetic neurons are colocalized within one ganglion capsule. Sympathetic MPG neurons are discriminated from parasympathetic ones by expression of low voltage-activated Ca2+ channels that primarily arise from T-type α1H isoform and contribute to the generation of low-threshold spikes. Until now, however, expression profiles of high voltage-activated (HVA) Ca2+ channels in these two populations of MPG neurons remain unknown. Thus, in the present study, we dissected out HVA Ca2+ channels using pharmacological and molecular biological tools. Reverse transcription-polymerase chain reaction analysis showed that MPG neurons contained transcripts encoding all of the known HVA Ca2+ channel isoforms (α1B, α1C, α1D, and α1E), with the exception of α1A. Western blot analysis and pharmacology with ω-agatoxin IVA (1 μM) confirmed that MPG neurons lack the α1A Ca2+ channels. Unexpectedly, the expression profile of HVA Ca2+ channel isoforms was identical in the sympathetic and parasympathetic neurons of the MPG. Of the total Ca2+ currents, ω-conotoxin GVIA-sensitive N-type (α1B) currents constituted 57 ± 5% (n = 9) and 60 ± 3% (n = 6), respectively; nimodipine-sensitive L-type (α1C and α1D) currents made up 17 ± 4% and 14 ± 2%, respectively; and nimodipine-resistant and ω-conotoxin GVIA-resistant R-type currents were 25 ± 3% and 22 ± 2%, respectively. The R-type Ca2+ currents were sensitive to NiCl2 (IC50 = 22 ± 0.1 μM) but not to SNX-482, which was able to potently (IC50 = 76 ± 0.4 nM) block the recombinant α1E/β2a/ α2δ Ca2+ currents expressed in human embryonic kidney 293 cells. Taken together, our data suggest that sympathetic and parasympathetic MPG neurons share a similar but unique profile of HVA Ca 2+ channel isoforms.

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