Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kawano, T; Zoga, V; McCallum, JB; Wu, HE; Gemes, G; Liang, MY; Abram, S; Kwok, WM; Hogan, QH; Sarantopoulos, CD.
ATP-SENSITIVE POTASSIUM CURRENTS IN RAT PRIMARY AFFERENT NEURONS: BIOPHYSICAL, PHARMACOLOGICAL PROPERTIES, AND ALTERATIONS BY PAINFUL NERVE INJURY
NEUROSCIENCE. 2009; 162(2): 431-443.
Doi: 10.1016/j.neuroscience.2009.04.076
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Gemes Geza
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- Abstract:
- ATP-sensitive potassium (K(ATP)) channels may be linked to mechanisms of pain after nerve injury, but remain under-investigated in primary afferents so far. We therefore characterized these channels in dorsal root ganglion (DRG) neurons, and tested whether they contribute to hyperalgesia after spinal nerve ligation (SNL). We compared K(ATP) channel properties between DRG somata classified by diameter into small or large, and by injury status into neurons from rats that either did or did not become hyperalgesic after SNL, or neurons from control animals. In cell-attached patches, we recorded basal K(ATP) channel opening in all neuronal subpopulations. However, higher open probabilities and longer open times were observed in large compared to small neurons. Following SNL, this channel activity was suppressed only in large neurons from hyperalgesic rats, but not from animals that did not develop hyperalgesia. In contrast, no alterations of channel activity developed in small neurons after axotomy. On the other hand, cell-free recordings showed similar ATP sensitivity, inward rectification and unitary conductance (70-80 pS) between neurons classified by size or injury status. Likewise, pharmacological sensitivity to the K(ATP) channel opener diazoxide, and to the selective blockers glibenclamide and tolbutamide, did not differ between groups. In large neurons, selective inhibition of whole-cell ATP-sensitive potassium channel current (I(K(ATP))) by glibenclamide depolarized resting membrane potential (RMP). The contribution of this current to RMP was also attenuated after painful axotomy. Using specific antibodies, we identified SUR1, SUR2, and Kir6.2 but not Kir6.1 subunits in DRGs. These findings indicate that functional K(ATP) channels are present in normal DRG neurons, wherein they regulate RMP. Alterations of these channels may be involved in the pathogenesis of neuropathic pain following peripheral nerve injury. Their biophysical and pharmacological properties are preserved even after axotomy, suggesting that K(ATP) channels in primary afferents remain available for therapeutic targeting against established neuropathic pain.
- Find related publications in this database (using NLM MeSH Indexing)
- ATP-Binding Cassette Transporters - biosynthesis
- Animals -
- Axotomy -
- Cell Size -
- Ganglia, Spinal - pathology
- Hyperalgesia - metabolism
- Ion Channel Gating -
- Male -
- Membrane Potentials -
- Neurons, Afferent - pathology
- Peripheral Nervous System Diseases - metabolism
- Potassium Channels, Inwardly Rectifying - biosynthesis
- Protein Subunits - biosynthesis
- Rats -
- Rats, Sprague-Dawley -
- Receptors, Drug - biosynthesis
- Spinal Nerves - injuries
- Find related publications in this database (Keywords)
- dorsal root ganglion
- spinal nerve ligation
- neuropathic pain
- diazoxide
- glibenclamide
- tolbutamide