Effects of phorbol-12,13-dibuterate on sodium currents and potassium currents in rat trigeminal ganglion neurons.
The effects of phorbol-12,13-dibuterate (PDBu) on total sodium current (I(Na)-total), tetrodotoxin-resistant sodium current (I(Na)-TTXr), 4-AP-sensitive potassium current (I(A)) and TEA-sensitive potassium current (I(K)) in trigeminal ganglion (TG) neurons were investigated. Whole-cell patch clamp techniques were used to record ion currents in cultured TG neurons of rats. Results revealed that 0.5 micromol/L PDBu reduced the amplitude of I(Na)-total by (38.3+/-4.5)% (n=6, P<0.05), but neither the G-V curve (control: V (0.5)=-17.1+/-4.3 mV, k=7.4+/-1.3; PDBu: V (0.5)=-15.9+/-5.9 mV, k=5.9+/-1.4; n=6, P>0.05) nor the inactivation rate constant (control: 3.6+/-0.9 ms; PDBu: 3.6+/-0.8 ms; n=6, P>0.05) was altered. 0.5 micromol/L PDBu could significantly increase the amplitude of I(Na)-TTXr by (37.2+/-3.2)% (n=9, P<0.05) without affecting the G-V curve (control: V (0.5)=-14.7+/-6.0 mV, k=6.9+/- 1.4; PDBu: V (0.5)=-11.1+/-5.3 mV, k=8.1+/-1.5; n=5, P>0.05) or the inactivation rate constant (control: 4.6+/-0.6 ms; PDBu: 4.2+/-0.5 ms; n=5, P>0.05). 0.5 mumol/L PDBu inhibited I(K) by (15.6+/-5.0) % (n=16, P<0.05), and V (0.5) was significantly altered from - 4.7+/-1.4 mV to -7.9 +/-1.8 mV (n=16, P<0.05). I(A) was not significantly affected by PDBu, 0.5 mumol/L PDBu decreased I(A) by only (0.3+/-3.2)% (n=5, P>0.05). It was concluded that PDBu inhibited I(Na)-total but enhanced I(Na)-TTXr, and inhibited I(K) without affecting I(A). These data suggested that the activation of PKC pathway could exert the actions.
Liu
Hui
H
Department of Pharmacology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. toliuhui@yahoo.com.cn
Hu
Benrong
B
Fu
Hui
H
Xiang
Jizhou
J
Liu
Lieju
L
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D062687:Sodium Channel Agonists; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects*; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D012668:Trigeminal Ganglion / Q000166:cytology*
D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D062687:Sodium Channel Agonists; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D015240:Phorbol 12,13-Dibutyrate; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D015761:4-Aminopyridine