The anti-nociceptive effect of BmK AS, a scorpion active polypeptide, and the possible mechanism on specifically modulating voltage-gated Na+ currents in primary afferent neurons.

Abstract

In the present study, we investigated the anti-nociceptive effect and the underlying mechanism of BmK AS, an active peptide purified from scorpion Buthus martensi Karsch. The results showed that BmK AS can significantly relieve formalin-induced two-phase spontaneous flinching response and carrageenan-induced mechanical hyperalgesia. Using the whole-cell patch-clamp recording, exposure of acutely isolated sensory neurons to 500 nM BmK AS produced a one-fold decrease in the number of action potentials (APs) evoked by a ramp of depolarizing current. To investigate the mechanism of action of BmK AS, isolated membrane current and Ca2+ influx on rat primary sensory neurons were examined. BmK AS produced insignificant effect on voltage-dependent I(K) and KCl or caffeine-induced Ca2+ influx, but caused remarkable suppressive effect on tetrodotoxin-resistant (TTX-R) and tetrodotoxin-sensitive (TTX-S) I(Na). Further experiments showed that BmK AS reduced the peak TTX-R and TTX-S Na+ conductance in a dose-dependent manner, prompted the voltage-dependent activation, and caused a negative shift of the steady-state inactivation of TTX-R and TTX-S I(Na). Thus, the present results indicate the anti-nociceptive response of BmK AS may be ascribed to its specific modulation of voltage-gated Na+ channels of sensory neurons.

• Authors: Jin Chen, Xing-Hua Feng, Jian Shi, Zhi-Yong Tan, Zhan-Tao Bai, Tong Liu, Yong-Hua Ji
• Journal: Peptides (Peptides) Vol. 27 Issue 9 Pg. 2182-92 (Sep 2006) ISSN: 0196-9781 [Print] United States
• PMID: 16716457 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• BmK AS polypeptide
• Peptides
• Ryanodine Receptor Calcium Release Channel
• Scorpion Venoms
• Sodium Channel Blockers
• Sodium Channels
• Formaldehyde
• Tetrodotoxin

Topics

• Action Potentials (drug effects)
• Analgesics (pharmacology)
• Animals
• Formaldehyde (metabolism, pharmacology)
• Ion Channel Gating (drug effects)
• Male
• Neurons, Afferent (cytology, drug effects, physiology)
• Pain Measurement
• Peptides (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Ryanodine Receptor Calcium Release Channel (drug effects, metabolism)
• Scorpion Venoms (pharmacology)
• Scorpions
• Sodium Channel Blockers (pharmacology)
• Sodium Channels (metabolism)
• Tetrodotoxin (metabolism)
• Time Factors