Agonistic effects of xanthines on tetrodotoxin-sensitive sodium channels in the rat dorsal root ganglion neurons

Parkhomenko, N. T.; Yatsenko, L. N.; Kuksenok, A. M.

doi:10.1007/bf02461240

Cited by 1 publication

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References 7 publications

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“…Applications of caffeine and theophylline, similarly to what was demonstrated earlier [11] with respect to the effect on sodium currents, resulted in shifts of the dependence graphs of both the sodium conductance and gating charge on the test potential toward more negative values of this potential. When 2 mM of these xanthines were present in the external solution, the shift was, on average, 5.4 ± 0.7 mV (n = 6 for each of the agents used).…”

Section: Resultssupporting

confidence: 76%

Gating currents of sodium channels in neurons of the rat trigeminal ganglia

Kostyuk

Parkhomenko

2004

Neurophysiology

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Using a voltage-clamp technique and intracellular dialysis, gating currents of sodium channels were first recorded and studied in neurons of the rat trigeminal ganglia. The rising phase of gating currents lasted 30 to 70 μsec; these currents decayed in a monoexponential manner with a time constant equal to that for activation of the sodium current. Voltage dependences for the gating charge and sodium conductance were also nearly identical. Analysis of the activation of sodium conductance demonstrated that the power n of the activation variable in the equation used changed from more than 6 to 3 at test potentials of -30 mV and 0 mV, respectively. It is hypothesized that, with a change in the test potential within this voltage range, the cooperativity of activation undergoes a twofold decrease. In the presence of 2 mM caffeine or theophylline in the external solution, curves of the voltage dependence of the gating charge and sodium conductance shifted toward more negative values of the test potential, by 5.4 ± 0.7 mV, the maximum gating charge increased by 8.4 ± 3.2%, and the slope factor for both curves decreased by 9.2 ± 3.4%. Since the above effects were identical for both xanthines and developed under conditions of constant intracellular dialysis, i.e., under conditions where the effect of a change in the intracellular calcium concentration was ruled out, the most probable reason for these effects is a direct action of the tested agents on sodium ion channels, which facilitates the movement of gating charges.

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Section: Resultssupporting

confidence: 76%