Capsaicin differentially modulates voltage-activated calcium channel currents in dorsal root ganglion neurones of rats

Tim Hagenacker, Frank Splettstoesser, Wolfgang Greffrath, Rolf Detlef Treede, Dietrich Busselberg

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

It is discussed whether capsaicin, an agonist of the pain mediating TRPV1 receptor, decreases or increases voltage-activated calcium channel (VACC) currents (ICa(V)). ICa(V) were isolated in cultured dorsal root ganglion (DRG) neurones of rats using the whole cell patch clamp method and Ba2+ as charge carrier. In large diameter neurones (>35μm), a concentration of 50μM was needed to reduce ICa(V) (activated by depolarizations to 0 mV) by 80%, while in small diameter neurones (≤30μm), the IC50 was 0.36 μM. This effect was concentration dependent with a threshold below 0.025 μM and maximal blockade (>80%) at 5μM. The current-voltage relation was shifted to the hyperpolarized direction with an increase of the current between -40 and -10mV and a decrease between 0 and +50 mV. Isolation of L-, N-, and T-type calcium channels resulted in differential effects when 0.1 μM capsaicin was applied. While T-type channel currents were equally reduced over the voltage range, L-type channel currents were additionally shifted to the hyperpolarized direction by 10 to 20 mV. N-type channel currents expressed either a shift (3 cells) or a reduction of the current (4 cells) or both (3 cells). Thus, capsaicin increases ICa(V) at negative and decreases ICa(V) at positive voltages by differentially affecting L-, N-, and T-type calcium channels. These effects of capsaicin on different VACCs in small DRG neurones, which most likely express the TRPV1 receptor, may represent another mechanism of action of the pungent substance capsaicin in addition to opening of TRPV1.

Original languageEnglish
Pages (from-to)74-85
Number of pages12
JournalBrain Research
Volume1062
Issue number1-2
DOIs
Publication statusPublished - 16 Nov 2005
Externally publishedYes

Fingerprint

Capsaicin
Spinal Ganglia
Calcium Channels
Neurons
T-Type Calcium Channels
N-Type Calcium Channels
Inhibitory Concentration 50
Pain
Direction compound
TRPV1 receptor

Keywords

  • Capsaicin
  • Dorsal root ganglion neurones
  • Electrophysiology
  • L-type calcium channel
  • N-type calcium channel
  • Pain
  • Patch clamp technique
  • Small diameter neurones
  • T-type calcium channel
  • TRPV1
  • Voltage-activated calcium channel current

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Developmental Biology
  • Clinical Neurology

Cite this

Capsaicin differentially modulates voltage-activated calcium channel currents in dorsal root ganglion neurones of rats. / Hagenacker, Tim; Splettstoesser, Frank; Greffrath, Wolfgang; Treede, Rolf Detlef; Busselberg, Dietrich.

In: Brain Research, Vol. 1062, No. 1-2, 16.11.2005, p. 74-85.

Research output: Contribution to journalArticle

Hagenacker, Tim ; Splettstoesser, Frank ; Greffrath, Wolfgang ; Treede, Rolf Detlef ; Busselberg, Dietrich. / Capsaicin differentially modulates voltage-activated calcium channel currents in dorsal root ganglion neurones of rats. In: Brain Research. 2005 ; Vol. 1062, No. 1-2. pp. 74-85.
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AU - Hagenacker, Tim

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AU - Greffrath, Wolfgang

AU - Treede, Rolf Detlef

AU - Busselberg, Dietrich

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AB - It is discussed whether capsaicin, an agonist of the pain mediating TRPV1 receptor, decreases or increases voltage-activated calcium channel (VACC) currents (ICa(V)). ICa(V) were isolated in cultured dorsal root ganglion (DRG) neurones of rats using the whole cell patch clamp method and Ba2+ as charge carrier. In large diameter neurones (>35μm), a concentration of 50μM was needed to reduce ICa(V) (activated by depolarizations to 0 mV) by 80%, while in small diameter neurones (≤30μm), the IC50 was 0.36 μM. This effect was concentration dependent with a threshold below 0.025 μM and maximal blockade (>80%) at 5μM. The current-voltage relation was shifted to the hyperpolarized direction with an increase of the current between -40 and -10mV and a decrease between 0 and +50 mV. Isolation of L-, N-, and T-type calcium channels resulted in differential effects when 0.1 μM capsaicin was applied. While T-type channel currents were equally reduced over the voltage range, L-type channel currents were additionally shifted to the hyperpolarized direction by 10 to 20 mV. N-type channel currents expressed either a shift (3 cells) or a reduction of the current (4 cells) or both (3 cells). Thus, capsaicin increases ICa(V) at negative and decreases ICa(V) at positive voltages by differentially affecting L-, N-, and T-type calcium channels. These effects of capsaicin on different VACCs in small DRG neurones, which most likely express the TRPV1 receptor, may represent another mechanism of action of the pungent substance capsaicin in addition to opening of TRPV1.

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