Faculty Collaboration Database

Opposing effects of spinal nerve ligation on calcium-activated potassium currents in axotomized and adjacent mammalian primary afferent neurons. Brain Res 2007 Feb 09;1132(1):84-99

Date

12/23/2006

Pubmed ID

17184741

Pubmed Central ID

PMC2692681

DOI

10.1016/j.brainres.2006.11.055

Scopus ID

2-s2.0-33846212798 (requires institutional sign-in at Scopus site)   46 Citations

Abstract

UNLABELLED: 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.

Author List

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

Authors

Quinn H. Hogan MD Professor in the Anesthesiology department at Medical College of Wisconsin
Wai-Meng Kwok PhD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Axotomy
Calcium
Calcium Signaling
Cell Size
Cells, Cultured
Ganglia, Spinal
Hyperalgesia
Ligation
Male
Membrane Potentials
Neurons, Afferent
Organ Culture Techniques
Patch-Clamp Techniques
Peripheral Nervous System Diseases
Potassium Channel Blockers
Potassium Channels, Calcium-Activated
Rats
Rats, Sprague-Dawley
Sciatic Neuropathy
Sodium Channel Blockers