Inflammation-induced changes in BK<sub>Ca</sub> currents in cutaneous dorsal root ganglion neurons from the adult rat
<p>Abstract</p> <p>Background</p> <p>Inflammation-induced sensitization of primary afferents is associated with a decrease in K<sup>+</sup> current. However, the type of K<sup>+</sup> current and basis for the decrease varies as a function of tar...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2012-07-01
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| Series: | Molecular Pain |
| Subjects: | |
| Online Access: | http://www.molecularpain.com/content/8/1/37 |
| _version_ | 1811330038090432512 |
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| author | Zhang Xiu-Lin Mok Lee-Peng Lee Kwan Charbonnet Marcel Gold Michael S |
| author_facet | Zhang Xiu-Lin Mok Lee-Peng Lee Kwan Charbonnet Marcel Gold Michael S |
| author_sort | Zhang Xiu-Lin |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Inflammation-induced sensitization of primary afferents is associated with a decrease in K<sup>+</sup> current. However, the type of K<sup>+</sup> current and basis for the decrease varies as a function of target of innervation. Because glabrous skin of the rat hindpaw is used often to assess changes in nociception in models of persistent pain, the purpose of the present study was to determine the type and extent to which K<sup>+</sup> currents contribute to the inflammation-induced sensitization of cutaneous afferents. Acutely dissociated retrogradely labeled cutaneous dorsal root ganglion neurons from naïve and inflamed (3 days post complete Freund’s adjuvant injection) rats were studied with whole cell and perforated patch techniques.</p> <p>Results</p> <p>Inflammation-induced sensitization of small diameter cutaneous neurons was associated with an increase in action potential duration and rate of decay of the afterhyperpolarization. However, no changes in voltage-gated K<sup>+</sup> currents were detected. In contrast, Ca<sup>2+</sup> modulated iberiotoxin sensitive and paxilline sensitive K<sup>+</sup> (BK<sub>Ca</sub>) currents were significantly smaller in small diameter IB4+ neurons. This decrease in current was not associated with a detectable change in total protein levels of the BK<sub>Ca</sub> channel α or β subunits. Single cell PCR analysis revealed a significant change in the pattern of expression of α subunit splice variants and β subunits that were consistent, at least in part, with inflammation-induced changes in the biophysical properties of BK<sub>Ca</sub> currents in cutaneous neurons.</p> <p>Conclusions</p> <p>Results of this study provide additional support for the conclusion that it may be possible, if not necessary to selectively treat pain arising from specific body regions. Because a decrease in BK<sub>Ca</sub> current appears to contribute to the inflammation-induced sensitization of cutaneous afferents, BK<sub>Ca</sub> channel openers may be effective for the treatment of inflammatory pain.</p> |
| first_indexed | 2024-04-13T15:54:21Z |
| format | Article |
| id | doaj.art-9b0beb6b91934477a00988f22914b680 |
| institution | Directory Open Access Journal |
| issn | 1744-8069 |
| language | English |
| last_indexed | 2024-04-13T15:54:21Z |
| publishDate | 2012-07-01 |
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| record_format | Article |
| series | Molecular Pain |
| spelling | doaj.art-9b0beb6b91934477a00988f22914b6802022-12-22T02:40:44ZengSAGE PublishingMolecular Pain1744-80692012-07-01813710.1186/1744-8069-8-37Inflammation-induced changes in BK<sub>Ca</sub> currents in cutaneous dorsal root ganglion neurons from the adult ratZhang Xiu-LinMok Lee-PengLee KwanCharbonnet MarcelGold Michael S<p>Abstract</p> <p>Background</p> <p>Inflammation-induced sensitization of primary afferents is associated with a decrease in K<sup>+</sup> current. However, the type of K<sup>+</sup> current and basis for the decrease varies as a function of target of innervation. Because glabrous skin of the rat hindpaw is used often to assess changes in nociception in models of persistent pain, the purpose of the present study was to determine the type and extent to which K<sup>+</sup> currents contribute to the inflammation-induced sensitization of cutaneous afferents. Acutely dissociated retrogradely labeled cutaneous dorsal root ganglion neurons from naïve and inflamed (3 days post complete Freund’s adjuvant injection) rats were studied with whole cell and perforated patch techniques.</p> <p>Results</p> <p>Inflammation-induced sensitization of small diameter cutaneous neurons was associated with an increase in action potential duration and rate of decay of the afterhyperpolarization. However, no changes in voltage-gated K<sup>+</sup> currents were detected. In contrast, Ca<sup>2+</sup> modulated iberiotoxin sensitive and paxilline sensitive K<sup>+</sup> (BK<sub>Ca</sub>) currents were significantly smaller in small diameter IB4+ neurons. This decrease in current was not associated with a detectable change in total protein levels of the BK<sub>Ca</sub> channel α or β subunits. Single cell PCR analysis revealed a significant change in the pattern of expression of α subunit splice variants and β subunits that were consistent, at least in part, with inflammation-induced changes in the biophysical properties of BK<sub>Ca</sub> currents in cutaneous neurons.</p> <p>Conclusions</p> <p>Results of this study provide additional support for the conclusion that it may be possible, if not necessary to selectively treat pain arising from specific body regions. Because a decrease in BK<sub>Ca</sub> current appears to contribute to the inflammation-induced sensitization of cutaneous afferents, BK<sub>Ca</sub> channel openers may be effective for the treatment of inflammatory pain.</p>http://www.molecularpain.com/content/8/1/37SensitizationVoltage clampNociceptorPerforated patch<it>in vitro</it> |
| spellingShingle | Zhang Xiu-Lin Mok Lee-Peng Lee Kwan Charbonnet Marcel Gold Michael S Inflammation-induced changes in BK<sub>Ca</sub> currents in cutaneous dorsal root ganglion neurons from the adult rat Molecular Pain Sensitization Voltage clamp Nociceptor Perforated patch <it>in vitro</it> |
| title | Inflammation-induced changes in BK<sub>Ca</sub> currents in cutaneous dorsal root ganglion neurons from the adult rat |
| title_full | Inflammation-induced changes in BK<sub>Ca</sub> currents in cutaneous dorsal root ganglion neurons from the adult rat |
| title_fullStr | Inflammation-induced changes in BK<sub>Ca</sub> currents in cutaneous dorsal root ganglion neurons from the adult rat |
| title_full_unstemmed | Inflammation-induced changes in BK<sub>Ca</sub> currents in cutaneous dorsal root ganglion neurons from the adult rat |
| title_short | Inflammation-induced changes in BK<sub>Ca</sub> currents in cutaneous dorsal root ganglion neurons from the adult rat |
| title_sort | inflammation induced changes in bk sub ca sub currents in cutaneous dorsal root ganglion neurons from the adult rat |
| topic | Sensitization Voltage clamp Nociceptor Perforated patch <it>in vitro</it> |
| url | http://www.molecularpain.com/content/8/1/37 |
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