Preferential Inhibition of I h in Rat Trigeminal Ganglion Neurons by an Organic Blocker

Preferential Inhibition of I h in Rat Trigeminal Ganglion Neurons by an Organic Blocker The potency and specificity of a novel organic I h current blocker DK-AH 268 (DK, Boehringer) was studied in cultured rat trigeminal ganglion neurons using whole-cell patch-clamp recording techniques. In neurons current-clamped at the resting potential, the application of 10 μm DK caused a slight hyperpolarization of the membrane potential and a small increase in the threshold for action potential discharge without any major change in the shape of the action potential. In voltage-clamped neurons, DK caused a reduction of a hyperpolarization-activated current. Current subtraction protocols revealed that the time-dependent, hyperpolarization-activated currents blocked by 10 μm DK or external Cs+ (3 mm) had virtually identical activation properties, suggesting that DK and Cs+ caused blockade of the same current, namely I h . The block of I h by DK was dose-dependent. At the intermediate and higher concentrations of DK (10 and 100 μm) a decrease in specificity was observed so that time-independent, inwardly rectifying and noninactivating, voltage-gated outward potassium currents were also reduced by DK but to a much lesser extent than the time-dependent, hyperpolarization-activated currents. Blockade of the time-dependent, hyperpolarization-activated currents by DK appeared to be use-dependent since it required hyperpolarization for the effect to take place. Relief of DK block was also aided by membrane hyperpolarization. Since both the time-dependent current blocked by DK and the Cs+-sensitive time-dependent current behaved as I h , we conclude that 10 μm DK can preferentially reduce I h without a major effect on other potassium currents. Thus, DK may be a useful agent in the investigation of the function of I h in neurons. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Preferential Inhibition of I h in Rat Trigeminal Ganglion Neurons by an Organic Blocker

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Publisher
Springer-Verlag
Copyright
Copyright © Inc. by 1997 Springer-Verlag New York
Subject
Life Sciences; Biochemistry, general; Human Physiology
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s002329900299
Publisher site
See Article on Publisher Site

Abstract

The potency and specificity of a novel organic I h current blocker DK-AH 268 (DK, Boehringer) was studied in cultured rat trigeminal ganglion neurons using whole-cell patch-clamp recording techniques. In neurons current-clamped at the resting potential, the application of 10 μm DK caused a slight hyperpolarization of the membrane potential and a small increase in the threshold for action potential discharge without any major change in the shape of the action potential. In voltage-clamped neurons, DK caused a reduction of a hyperpolarization-activated current. Current subtraction protocols revealed that the time-dependent, hyperpolarization-activated currents blocked by 10 μm DK or external Cs+ (3 mm) had virtually identical activation properties, suggesting that DK and Cs+ caused blockade of the same current, namely I h . The block of I h by DK was dose-dependent. At the intermediate and higher concentrations of DK (10 and 100 μm) a decrease in specificity was observed so that time-independent, inwardly rectifying and noninactivating, voltage-gated outward potassium currents were also reduced by DK but to a much lesser extent than the time-dependent, hyperpolarization-activated currents. Blockade of the time-dependent, hyperpolarization-activated currents by DK appeared to be use-dependent since it required hyperpolarization for the effect to take place. Relief of DK block was also aided by membrane hyperpolarization. Since both the time-dependent current blocked by DK and the Cs+-sensitive time-dependent current behaved as I h , we conclude that 10 μm DK can preferentially reduce I h without a major effect on other potassium currents. Thus, DK may be a useful agent in the investigation of the function of I h in neurons.

Journal

The Journal of Membrane BiologySpringer Journals

Published: Nov 15, 1997

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