Opposing effects of spinal nerve ligation on calcium-activated potassium currents in axotomized and adjacent mammalian primary afferent neurons.

Opposing effects of spinal nerve ligation on calcium-activated potassium currents in axotomized and adjacent mammalian primary afferent neurons. Research Abstract Details 

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Opposing effects of spinal nerve ligation on calcium-activated potassium currents in axotomized and adjacent mammalian primary afferent neurons. Abstract Text:

Constantine D Sarantopoulos,J Bruce McCallum,Marcel Rigaud,Andreas Fuchs,Wai-Meng Kwok,Quinn H Hogan,

Calcium-activated potassium channels regulate AHP and excitability in neurons. Since we have previously shown that axotomy decreases I(Ca) in DRG neurons, we investigated the association between I(Ca) and K((Ca)) currents in control medium-sized (30-39 microM) neurons, as well as axotomized L5 or adjacent L4 DRG neurons from hyperalgesic rats following L5 SNL. Currents in response to AP waveform voltage commands were recorded first in Tyrode's solution and sequentially after: 1) blocking Na(+) current with NMDG and TTX; 2) addition of K((Ca)) blockers with a combination of apamin 1 microM, iberiotoxin 200 nM, and clotrimazole 500 nM; 3) blocking remaining K(+) current with the addition of 4-AP, TEA-Cl, and glibenclamide; and 4) blocking I(Ca) with cadmium. In separate experiments, currents were evoked (HP -60 mV, 200 ms square command pulses from -100 to +50 mV) while ensuring high levels of activation of I(K(Ca)) by clamping cytosolic Ca(2+) concentration with pipette solution in which Ca(2+) was buffered to 1 microM. This revealed I(K(Ca)) with components sensitive to apamin, clotrimazole and iberiotoxin. SNL decreases total I(K(Ca)) in axotomized (L5) neurons, but increases total I(K(Ca)) in adjacent (L4) DRG neurons. All I(K(Ca)) subtypes are decreased by axotomy, but iberiotoxin-sensitive and clotrimazole-sensitive current densities are increased in adjacent L4 neurons after SNL. In an additional set of experiments we found that small-sized control DRG neurons also expressed iberiotoxin-sensitive currents, which are reduced in both axotomized (L5) and adjacent (L4) neurons. CONCLUSIONS: Axotomy decreases I(K(Ca)) due to a direct effect on K((Ca)) channels. Axotomy-induced loss of I(Ca) may further potentiate current reduction. This reduction in I(K(Ca)) may contribute to elevated excitability after axotomy. Adjacent neurons (L4 after SNL) exhibit increased I(K(Ca)) current.

Opposing effects of spinal nerve ligation on calcium-activated potassium currents in axotomized and adjacent mammalian primary afferent neurons. Publishing Authors By Initials

CD Sarantopoulos,JB McCallum,M Rigaud,A Fuchs,WM Kwok,QH Hogan,

For similar chemical actions and uses: pharmacologic actions: molecular mechanisms of pharmacological action: membrane transport modulators: sodium channel blockers research abstracts see: chemical actions and uses: pharmacologic actions: molecular mechanisms of pharmacological action: membrane transport modulators: sodium channel blockers research

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Opposing effects of spinal nerve ligation on calcium-activated potassium currents in axotomized and adjacent mammalian primary afferent neurons. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Brain research

VOLUME: 1132

Page Numbers: 84-99

Journal Abbreviation: Brain Res.

ISSN: 0006-8993

DAY: 20

MONTH: 12

YEAR: 2006

Opposing effects of spinal nerve ligation on calcium-activated potassium currents in axotomized and adjacent mammalian primary afferent neurons. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 45503

Opposing effects of spinal nerve ligation on calcium-activated potassium currents in axotomized and adjacent mammalian primary afferent neurons. Keywords Mesh Terms:

KEYWORDS: Sodium Channel Blockers

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Opposing effects of spinal nerve ligation on calcium-activated potassium currents in axotomized and adjacent mammalian primary afferent neurons. Information

Substance Name: Calcium

Registry Number: 7440-70-2

Grant and Affiliation Information for Opposing effects of spinal nerve ligation on calcium-activated potassium currents in axotomized and adjacent mammalian primary afferent neurons.

AFFILIATION: Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. csar@mcw.edu

Country: Netherlands

AGENCY: United States PHS

GRANT: S049420A

ACRONYM: NS

MEDLINETA: Brain Res

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