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. 2019 Jan-Feb;10(1):49-58.
doi: 10.32598/bcn.9.10.350. Epub 2019 Jan 1.

Characterization of Functional Effects of Two New Active Fractions Isolated From Scorpion Venom on Neuronal Ca2+ Spikes: A Possible Action on Ca2+-Dependent Dependent K+ Channels

Hanieh Tamadon  1 , Zahra Ghasemi  2 , Fatemeh Ghasemi  1 , Narges Hosseinmardi  1 , Hossein Vatanpour  3 , Mahyar Janahmadi  1
Affiliations

Characterization of Functional Effects of Two New Active Fractions Isolated From Scorpion Venom on Neuronal Ca2+ Spikes: A Possible Action on Ca2+-Dependent Dependent K+ Channels

Hanieh Tamadon et al. Basic Clin Neurosci. 2019 Jan-Feb.

Abstract

Introduction: It is a long time that natural toxin research is conducted to unlock the medical potential of toxins. Although venoms-toxins cause pathophysiological conditions, they may be effective to treat several diseases. Since toxins including scorpion toxins target voltage-gated ion channels, they may have profound effects on excitable cells. Therefore, elucidating the cellular and electrophysiological impacts of toxins, particularly scorpion toxins would be helpful in future drug development opportunities.

Methods: Intracellular recording was made from F1 cells of Helix aspersa in the presence of calcium Ringer solution in which Na+ and K+ channels were blocked. Then, the modulation of channel function in the presence of extracellular application of F4 and F6 toxins and kaliotoxin (KTX; 50 nM and 1 μM) was examined by assessing the electrophysiological characteristics of calcium spikes.

Results: The two active toxin fractions, similar to KTX, a known Ca2+-activated K+ channel blocker, reduced the amplitude of AHP, enhanced the firing frequency of calcium spikes and broadened the duration of Ca2+ spikes. Therefore, it might be inferred that these two new fractions induce neuronal hyperexcitability possibly, in part, by blocking calcium-activated potassium channel current. However, this supposition requires further investigation using voltage clamping technique.

Conclusion: These toxin fractions may act as blocker of calcium-activated potassium channels.

Keywords: Buthotus schach; Calcium spike; Intracellular recording; Scorpion Venom.

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Conflict of interest statement

Conflict of interest The authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
Effects of two different concentrations of F4 and F6 fractions isolated from Buthotus schach scorpion venom and KTX on the spontaneous calcium spike firing Extracellular application of either F4 and F6 or KTX resulted in the neuronal hyperexcitability.
Figure 2.
Figure 2.
Effect of two neurotoxins and KTX on the AHP amplitude and the half-width of Ca2+ spike (A) Application of either the two active fractions, F4 and F6, or KTX caused a significant reduction in the AHP amplitude; (B) Neuronal exposure to all applied neurotoxins led to a significant spike broadening, except KTX 50 nM, which reduced the duration of calcium spike. (C) Superimposed Ca2+ spikes in the control condition and after application of the two active toxin fractions and KTX. (B) *Indicates significant difference between the control group and all neurotoxins treated groups (P<0.001, P<0.01); # shows significant difference between KTX and the two active toxin fractions (P<0.05, P<0.01, P<0.001).
Figure 3.
Figure 3.
Effect of F4, F6, and KTX on the F1 cell electrophysiological properties The impact of toxins on the resting membrane potential (A), action potential duration (B), and spike frequency (C); * indicates significant difference between the control group and all neurotoxins treated groups (P<0.05, P<0.01, P<0.001); # shows significant difference between KTX and the two active toxin fractions (P<0.05, P<0.01, P<0.001)
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