Preferential Inhibition of I
h
in Rat Trigeminal Ganglion Neurons by an Organic Blocker |
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Authors: | D Janigro ME Martenson TK Baumann |
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Institution: | (1) Division of Neurosurgery and Department of Physiology and Pharmacology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201-3098, USA, US |
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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.
Received: 3 March 1995/Revised: 8 July 1997 |
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Keywords: | : Whole-cell patch-clamp — Time-dependent hyperpolarization-activated current — Ih— Block — K+ channels |
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