Capsaicin differentially modulates voltage-activated calcium channel currents in dorsal root ganglion neurones of rats.
It is discussed whether capsaicin, an agonist of the pain mediating TRPV1 receptor, decreases or increases voltage-activated calcium channel (VACC) currents (I(Ca(V))). I(Ca(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 (>35 micorm), a concentration of 50 microM was needed to reduce I(Ca(V)) (activated by depolarizations to 0 mV) by 80%, while in small diameter neurones (< or =30 microm), the IC50 was 0.36 microM. This effect was concentration dependent with a threshold below 0.025 microM and maximal blockade (>80%) at 5 microM. The current-voltage relation was shifted to the hyperpolarized direction with an increase of the current between -40 and -10 mV and a decrease between 0 and +50 mV. Isolation of L-, N-, and T-type calcium channels resulted in differential effects when 0.1 microM 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 I(Ca(V)) at negative and decreases I(Ca(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.
Hagenacker
Tim
T
Institut für Physiologie, Universitätsklinikum Essen, Universität Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany.
Splettstoesser
Frank
F
Greffrath
Wolfgang
W
Treede
Rolf-Detlef
RD
Büsselberg
Dietrich
D
D000818:Animals; D015220:Calcium Channels / Q000145:classification / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology*; D048429:Cell Size; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D015290:Second Messenger Systems / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D050916:TRPV Cation Channels / Q000819:agonists
D015220:Calcium Channels; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D002211:Capsaicin