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Scorpion Toxin, BmP01, Induces Pain by Targeting TRPV1 Channel.

Hakim MA, Jiang W, Luo L, Li B, Yang S, Song Y, Lai R - Toxins (Basel) (2015)

Bottom Line: Furthermore, OPEN ACCESS Toxins 2015, 7 3672 BmP01 evoked currents on TRPV1-expressed HEK293T cells, but not on HEK293T cells without TRPV1.These results suggest that (1) BmP01 is one of the pain-inducing agents in scorpion venoms; and (2) BmP01 induces pain by acting on TRPV1.To our knowledge, this is the first report about a scorpion toxin that produces pain by targeting TRPV1.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. hakeem.geb.ru@gmail.com.

ABSTRACT
The intense pain induced by scorpion sting is a frequent clinical manifestation. To date, there is no established protocol with significant efficacy to alleviate the pain induced by scorpion envenomation. One of the important reasons is that, little information on pain-inducing compound from scorpion venoms is available. Here, a pain-inducing peptide (BmP01) has been identified and characterized from the venoms of scorpion (Mesobuthus martensii). In an animal model, intraplantar injection of BmP01 in mouse hind paw showed significant acute pain in wild type (WT) mice but not in TRPV1 knock-out (TRPV1 KO) mice during 30 min recording. BmP01 evoked currents in WT dorsal root ganglion (DRG) neurons but had no effect on DRG neurons of TRPV1 KO mice. Furthermore, OPEN ACCESS Toxins 2015, 7 3672 BmP01 evoked currents on TRPV1-expressed HEK293T cells, but not on HEK293T cells without TRPV1. These results suggest that (1) BmP01 is one of the pain-inducing agents in scorpion venoms; and (2) BmP01 induces pain by acting on TRPV1. To our knowledge, this is the first report about a scorpion toxin that produces pain by targeting TRPV1. Identification of a pain-inducing compound may facilitate treating pain induced by scorpion envenomation.

No MeSH data available.


Related in: MedlinePlus

Effects of BmP01 on mouse Kv channels. (A) 1 mM BmP01 did not inhibit the mKv1.1 currents; (B) 10 μM of BmP01 inhibited the currents on mKv1.3; (C) the concentration–response relationship of BmP01 against mKv1.3 yielded an EC50 of 269.15 ± 12.69 nM (n = 10); and (D) on-rate and off-rate of BmP01 interacting with mKv1.1.
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toxins-07-03671-f003: Effects of BmP01 on mouse Kv channels. (A) 1 mM BmP01 did not inhibit the mKv1.1 currents; (B) 10 μM of BmP01 inhibited the currents on mKv1.3; (C) the concentration–response relationship of BmP01 against mKv1.3 yielded an EC50 of 269.15 ± 12.69 nM (n = 10); and (D) on-rate and off-rate of BmP01 interacting with mKv1.1.

Mentions: Since the peptide, BmP01, from Buthus martensii, has been previously reported as rat Kv1.1 and human Kv1.3 channel blocker, we firstly tested the function of native BmP01 on mKv1.1 and mKv1.3 channels. In electrophysiology, application of 10 µM of BmP01 inhibited mKv1.3 currents (Figure 3B), while 1 mM of BmP01 showed no significant effect on mKv1.1 (Figure 3A). To determine the potency of the toxin on mKv1.3, we performed further experiment to measure the concentration—response relationship. The data dots fitted by Hill equation yielded an EC50 of 269.15 ± 12.69 nM (Figure 3C). To establish on-rate and off-rate of toxin binding, current amplitudes were fitted by a single-exponential function. In the presence of 10 µM BmP01, the time constants of inhibition and washing were (5.04 ± 0.86 s) and (6.22 ± 0.15 s), respectively (Figure 3D). These findings suggested that the high affinity might be caused by the rapid onset of the BmP01. Assumingly, there may have evolutionary changes of ion channels in murine, which make BmP01 to exhibit inhibitory activity on rKv1.1 but not on mKv1.1. According to these findings in this work, the pain-producing mechanism of BmP01 still remains un-clear; hence, the following experiments were designed and carried out.


Scorpion Toxin, BmP01, Induces Pain by Targeting TRPV1 Channel.

Hakim MA, Jiang W, Luo L, Li B, Yang S, Song Y, Lai R - Toxins (Basel) (2015)

Effects of BmP01 on mouse Kv channels. (A) 1 mM BmP01 did not inhibit the mKv1.1 currents; (B) 10 μM of BmP01 inhibited the currents on mKv1.3; (C) the concentration–response relationship of BmP01 against mKv1.3 yielded an EC50 of 269.15 ± 12.69 nM (n = 10); and (D) on-rate and off-rate of BmP01 interacting with mKv1.1.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4591660&req=5

toxins-07-03671-f003: Effects of BmP01 on mouse Kv channels. (A) 1 mM BmP01 did not inhibit the mKv1.1 currents; (B) 10 μM of BmP01 inhibited the currents on mKv1.3; (C) the concentration–response relationship of BmP01 against mKv1.3 yielded an EC50 of 269.15 ± 12.69 nM (n = 10); and (D) on-rate and off-rate of BmP01 interacting with mKv1.1.
Mentions: Since the peptide, BmP01, from Buthus martensii, has been previously reported as rat Kv1.1 and human Kv1.3 channel blocker, we firstly tested the function of native BmP01 on mKv1.1 and mKv1.3 channels. In electrophysiology, application of 10 µM of BmP01 inhibited mKv1.3 currents (Figure 3B), while 1 mM of BmP01 showed no significant effect on mKv1.1 (Figure 3A). To determine the potency of the toxin on mKv1.3, we performed further experiment to measure the concentration—response relationship. The data dots fitted by Hill equation yielded an EC50 of 269.15 ± 12.69 nM (Figure 3C). To establish on-rate and off-rate of toxin binding, current amplitudes were fitted by a single-exponential function. In the presence of 10 µM BmP01, the time constants of inhibition and washing were (5.04 ± 0.86 s) and (6.22 ± 0.15 s), respectively (Figure 3D). These findings suggested that the high affinity might be caused by the rapid onset of the BmP01. Assumingly, there may have evolutionary changes of ion channels in murine, which make BmP01 to exhibit inhibitory activity on rKv1.1 but not on mKv1.1. According to these findings in this work, the pain-producing mechanism of BmP01 still remains un-clear; hence, the following experiments were designed and carried out.

Bottom Line: Furthermore, OPEN ACCESS Toxins 2015, 7 3672 BmP01 evoked currents on TRPV1-expressed HEK293T cells, but not on HEK293T cells without TRPV1.These results suggest that (1) BmP01 is one of the pain-inducing agents in scorpion venoms; and (2) BmP01 induces pain by acting on TRPV1.To our knowledge, this is the first report about a scorpion toxin that produces pain by targeting TRPV1.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. hakeem.geb.ru@gmail.com.

ABSTRACT
The intense pain induced by scorpion sting is a frequent clinical manifestation. To date, there is no established protocol with significant efficacy to alleviate the pain induced by scorpion envenomation. One of the important reasons is that, little information on pain-inducing compound from scorpion venoms is available. Here, a pain-inducing peptide (BmP01) has been identified and characterized from the venoms of scorpion (Mesobuthus martensii). In an animal model, intraplantar injection of BmP01 in mouse hind paw showed significant acute pain in wild type (WT) mice but not in TRPV1 knock-out (TRPV1 KO) mice during 30 min recording. BmP01 evoked currents in WT dorsal root ganglion (DRG) neurons but had no effect on DRG neurons of TRPV1 KO mice. Furthermore, OPEN ACCESS Toxins 2015, 7 3672 BmP01 evoked currents on TRPV1-expressed HEK293T cells, but not on HEK293T cells without TRPV1. These results suggest that (1) BmP01 is one of the pain-inducing agents in scorpion venoms; and (2) BmP01 induces pain by acting on TRPV1. To our knowledge, this is the first report about a scorpion toxin that produces pain by targeting TRPV1. Identification of a pain-inducing compound may facilitate treating pain induced by scorpion envenomation.

No MeSH data available.


Related in: MedlinePlus