Allosteric interactions between receptor site 3 and 4 of voltage-gated sodium channels: a novel perspective for the underlying mechanism of scorpion sting-induced pain
AbstractBackground BmK I, a site-3-specific modulator of voltage-gated sodium channels (VGSCs), causes pain and hyperalgesia in rats, while BmK IT2, a site-4-specific modulator of VGSCs, suppresses pain-related responses. A stronger pain-related effect has been previously attributed to Buthus marten...
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ftdoajarticles:oai:doaj.org/article:d553c27709344fc78fdfd05dc0abab3a 2023-05-15T15:10:55+02:00 Allosteric interactions between receptor site 3 and 4 of voltage-gated sodium channels: a novel perspective for the underlying mechanism of scorpion sting-induced pain Yi-Jun Feng Qi Feng Jie Tao Rong Zhao Yong-Hua Ji 2015-11-01T00:00:00Z https://doi.org/10.1186/s40409-015-0043 https://doaj.org/article/d553c27709344fc78fdfd05dc0abab3a EN eng SciELO http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992015000100347&lng=en&tlng=en https://doaj.org/toc/1678-9199 1678-9199 doi:10.1186/s40409-015-0043 https://doaj.org/article/d553c27709344fc78fdfd05dc0abab3a Journal of Venomous Animals and Toxins including Tropical Diseases, Vol 21, Iss 0, Pp 5-5 (2015) BmK I BmK IT2 Synergistic effect Allosteric interactions Arctic medicine. Tropical medicine RC955-962 Toxicology. Poisons RA1190-1270 Zoology QL1-991 article 2015 ftdoajarticles https://doi.org/10.1186/s40409-015-0043 2022-12-31T01:52:36Z AbstractBackground BmK I, a site-3-specific modulator of voltage-gated sodium channels (VGSCs), causes pain and hyperalgesia in rats, while BmK IT2, a site-4-specific modulator of VGSCs, suppresses pain-related responses. A stronger pain-related effect has been previously attributed to Buthus martensi Karsch (BmK) venom, which points out the joint pharmacological effect in the crude venom.Methods In order to detect the joint effect of BmK I and BmK IT2 on ND7-23 cells, the membrane current was measured by whole cell recording. BmK I and BmK IT2 were applied successively and jointly, and the synergistic modulations of VGSCs on ND7-23 cells were detected.Results Larger peak I Na and more negative half-activation voltage were elicited by joint application of BmK I and BmK IT2 than by application of BmK I or BmK IT2 alone. Compared to the control, co-applied BmK I and BmK IT2 also significantly prolonged the time constant of inactivation.Conclusions Our results indicated that site-4 toxin (BmK IT2) could enhance the pharmacological effect induced by site-3 toxin (BmK I), suggesting a stronger effect elicited by both toxins that alone usually exhibit opposite pharmacological effects, which is related to the allosteric interaction between receptor site 3 and site 4. Meanwhile, these results may bring a novel perspective for exploring the underlying mechanisms of scorpion sting-induced pain. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
BmK I BmK IT2 Synergistic effect Allosteric interactions Arctic medicine. Tropical medicine RC955-962 Toxicology. Poisons RA1190-1270 Zoology QL1-991 |
spellingShingle |
BmK I BmK IT2 Synergistic effect Allosteric interactions Arctic medicine. Tropical medicine RC955-962 Toxicology. Poisons RA1190-1270 Zoology QL1-991 Yi-Jun Feng Qi Feng Jie Tao Rong Zhao Yong-Hua Ji Allosteric interactions between receptor site 3 and 4 of voltage-gated sodium channels: a novel perspective for the underlying mechanism of scorpion sting-induced pain |
topic_facet |
BmK I BmK IT2 Synergistic effect Allosteric interactions Arctic medicine. Tropical medicine RC955-962 Toxicology. Poisons RA1190-1270 Zoology QL1-991 |
description |
AbstractBackground BmK I, a site-3-specific modulator of voltage-gated sodium channels (VGSCs), causes pain and hyperalgesia in rats, while BmK IT2, a site-4-specific modulator of VGSCs, suppresses pain-related responses. A stronger pain-related effect has been previously attributed to Buthus martensi Karsch (BmK) venom, which points out the joint pharmacological effect in the crude venom.Methods In order to detect the joint effect of BmK I and BmK IT2 on ND7-23 cells, the membrane current was measured by whole cell recording. BmK I and BmK IT2 were applied successively and jointly, and the synergistic modulations of VGSCs on ND7-23 cells were detected.Results Larger peak I Na and more negative half-activation voltage were elicited by joint application of BmK I and BmK IT2 than by application of BmK I or BmK IT2 alone. Compared to the control, co-applied BmK I and BmK IT2 also significantly prolonged the time constant of inactivation.Conclusions Our results indicated that site-4 toxin (BmK IT2) could enhance the pharmacological effect induced by site-3 toxin (BmK I), suggesting a stronger effect elicited by both toxins that alone usually exhibit opposite pharmacological effects, which is related to the allosteric interaction between receptor site 3 and site 4. Meanwhile, these results may bring a novel perspective for exploring the underlying mechanisms of scorpion sting-induced pain. |
format |
Article in Journal/Newspaper |
author |
Yi-Jun Feng Qi Feng Jie Tao Rong Zhao Yong-Hua Ji |
author_facet |
Yi-Jun Feng Qi Feng Jie Tao Rong Zhao Yong-Hua Ji |
author_sort |
Yi-Jun Feng |
title |
Allosteric interactions between receptor site 3 and 4 of voltage-gated sodium channels: a novel perspective for the underlying mechanism of scorpion sting-induced pain |
title_short |
Allosteric interactions between receptor site 3 and 4 of voltage-gated sodium channels: a novel perspective for the underlying mechanism of scorpion sting-induced pain |
title_full |
Allosteric interactions between receptor site 3 and 4 of voltage-gated sodium channels: a novel perspective for the underlying mechanism of scorpion sting-induced pain |
title_fullStr |
Allosteric interactions between receptor site 3 and 4 of voltage-gated sodium channels: a novel perspective for the underlying mechanism of scorpion sting-induced pain |
title_full_unstemmed |
Allosteric interactions between receptor site 3 and 4 of voltage-gated sodium channels: a novel perspective for the underlying mechanism of scorpion sting-induced pain |
title_sort |
allosteric interactions between receptor site 3 and 4 of voltage-gated sodium channels: a novel perspective for the underlying mechanism of scorpion sting-induced pain |
publisher |
SciELO |
publishDate |
2015 |
url |
https://doi.org/10.1186/s40409-015-0043 https://doaj.org/article/d553c27709344fc78fdfd05dc0abab3a |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Journal of Venomous Animals and Toxins including Tropical Diseases, Vol 21, Iss 0, Pp 5-5 (2015) |
op_relation |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992015000100347&lng=en&tlng=en https://doaj.org/toc/1678-9199 1678-9199 doi:10.1186/s40409-015-0043 https://doaj.org/article/d553c27709344fc78fdfd05dc0abab3a |
op_doi |
https://doi.org/10.1186/s40409-015-0043 |
_version_ |
1766341854100455424 |