Painful Peripheral Nerve Injury Decreases Calcium Current in Axotomized Sensory Neurons

McCallum, J. Bruce; Kwok, Wai‐Meng; Sapunar, Damir; Fuchs, Andreas; Hogan, Quinn H.

doi:10.1097/00000542-200607000-00026

Cited by 64 publications

(79 citation statements)

References 41 publications

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“…However, we have also demonstrated a depression of Ca 2+ channel function after axotomy. 11 It seems that the dominant effect of axotomy is a diminished inward Ca 2+ flux, as our current findings show decreased duration and amplitude of the Ca 2+ transient in L5 neurons after SNL ( fig. 7).…”

Section: Discussionsupporting

confidence: 58%

“…9 Our previous data have identified reduced Ca 2+ influx through high-and low-voltageactivated Ca 2+ channels of primary sensory neurons after painful peripheral nerve injury. 5,10,11 We have further observed that resting Ca 2+ levels are lower in sensory neurons after injury. 12 The influence of these alterations on depolarization-induced Ca 2+ transients is unknown.…”

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confidence: 62%

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Painful Nerve Injury Shortens the Intracellular Ca2+ Signal in Axotomized Sensory Neurons of Rats

2007

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Section: Discussionsupporting

confidence: 58%

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confidence: 62%

Painful Nerve Injury Shortens the Intracellular Ca2+ Signal in Axotomized Sensory Neurons of Rats

2007

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“…Because BK channels control neurotransmitter release [86] and inter-neuronal glutaminergic synaptic efficacy [72], it is also likely that loss of BK currents in small and medium sized neurons after axotomy may enhance synaptic transmission of afferent signaling, as well. In addition to loss of I K(Ca) currents in a manner directly related to nerve injury, we have also previously shown that neuropathy decreases I Ca [60,61], a mechanism that may reduce the activation of K (Ca) currents in addition to the direct effect of SNL, thus leading to a higher enhancement of excitability.…”

Section: Discussionmentioning

confidence: 91%

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

Sarantopoulos¹,

McCallum²,

Rigaud³

et al. 2007

Brain Research

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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 μM) 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 1μM, 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 to1μM. 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.

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“…Both the reduction of HVA Ca 2ϩ currents and the increase in T-type currents in DRG neurons have been reported in animal models of persistent pain (Abdulla and Smith 2001a;Jagodic et al 2008Jagodic et al , 2007McCallum et al 2006). The reduction of HVA Ca 2ϩ currents may attenuate Ca 2ϩ -sensitive K ϩ currents and, in turn, increase neuronal excitability (Abdulla and Smith 2001b;Hogan 2007).…”

Section: Fig 7 Neuronal Excitability Is Increased In Small Ib4mentioning

confidence: 96%

Effects of familial hemiplegic migraine type 1 mutation T666M on voltage-gated calcium channel activities in trigeminal ganglion neurons

Tao

Liu

Xiao

et al. 2012

Journal of Neurophysiology

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Cao YQ. Effects of familial hemiplegic migraine type 1 mutation T666M on voltagegated calcium channel activities in trigeminal ganglion neurons. J Neurophysiol 107: 1666 -1680, 2012. First published December 21, 2011 doi:10.1152/jn.00551.2011.-Familial hemiplegic migraine type 1 (FHM-1), a rare hereditary form of migraine with aura and hemiparesis, serves as a good model for exploring migraine pathophysiology. The FHM-1 gene encodes the pore-forming Ca V 2.1 subunit of human P/Q-type voltage-gated Ca 2ϩ channels (VGCCs). Some FHM-1 mutations result in a decrease of whole cell P/Q-type current density in transfected cells/neurons. Questions remain as to whether and how these mutations may increase the gain of the trigeminal nociceptive pathway underlying migraine headache. Here, we investigated the effects of T666M, the most frequently occurring FHM-1 mutation, on VGCC currents and neuronal excitability in trigeminal ganglion (TG) neurons. We expressed human wild-type and T666M Ca V 2.1 subunits in cultured TG neurons from Ca V 2.1 knockout mice and recorded whole cell VGCC currents in transfected neurons. Currents mediated by individual VGCC subtypes were dissected according to their pharmacological and biophysical properties. TG neurons were sorted into three subpopulations based on their soma size and their affinity to isolectin B4 (IB4). We found that the T666M mutation did not affect total or surface expression of Ca V 2.1 proteins but caused a profound reduction of P/Q-type current in all subtypes of TG neurons. Interestingly, a compensatory increase in Ca V 3.2-mediated low-voltageactivated T-type currents only occurred in small IB4-negative (IB4 Ϫ ) TG neurons expressing T666M subunits. Current-clamp recordings showed that the T666M mutation resulted in hyperexcitability of the small IB4 Ϫ TG population. Taken together, our results suggest a possible scenario through which FHM-1 mutations might increase the gain of the trigeminal nociceptive pathway.

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Painful Peripheral Nerve Injury Decreases Calcium Current in Axotomized Sensory Neurons

Cited by 64 publications

References 41 publications

Painful Nerve Injury Shortens the Intracellular Ca2+ Signal in Axotomized Sensory Neurons of Rats

Painful Nerve Injury Shortens the Intracellular Ca2+ Signal in Axotomized Sensory Neurons of Rats

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

Effects of familial hemiplegic migraine type 1 mutation T666M on voltage-gated calcium channel activities in trigeminal ganglion neurons

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