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Novel mechanism of blocking axonal Na(+) channels by three macrocyclic polyamine analogues and two spider toxins.
Br J Pharmacol. 2001 Jan; 132(1):63-72.BJ

Abstract

1. The mechanism of Na(+) channel block by three macrocyclic polyamine derivatives and two spider toxins was studied with voltage clamp and internal perfusion method in squid axons. 2. All these chemicals specifically block Na(+) channels in the open state only from the internal surface, and do not affect K(+) channels. 3. The blocking effect is enhanced as the depolarizing pulse becomes larger. Blocked channels are unable to shift to the inactivated state. 4. In the case of cyclam and guanidyl-side armed cyclam (G-cyclam), quick release of these chemicals from the binding sites is proven by the increase in the tail current and prolongation of the time course of the off gating current. On the other hand, in the presence of N-4 and the spider toxins, their detachment was delayed significantly. 5. Molecular requirements for the block of Na(+) channels by these molecules are the presence of positive charge and hydrophobicity.

Authors+Show Affiliations

Department of Physiology, School of Medicine, Hiroshima University, Hiroshima 734-8551, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11156562

Citation

Yakehiro, M, et al. "Novel Mechanism of Blocking Axonal Na(+) Channels By Three Macrocyclic Polyamine Analogues and Two Spider Toxins." British Journal of Pharmacology, vol. 132, no. 1, 2001, pp. 63-72.
Yakehiro M, Furukawa Y, Koike T, et al. Novel mechanism of blocking axonal Na(+) channels by three macrocyclic polyamine analogues and two spider toxins. Br J Pharmacol. 2001;132(1):63-72.
Yakehiro, M., Furukawa, Y., Koike, T., Kimura, E., Nakajima, T., Yamaoka, K., & Seyama, I. (2001). Novel mechanism of blocking axonal Na(+) channels by three macrocyclic polyamine analogues and two spider toxins. British Journal of Pharmacology, 132(1), 63-72.
Yakehiro M, et al. Novel Mechanism of Blocking Axonal Na(+) Channels By Three Macrocyclic Polyamine Analogues and Two Spider Toxins. Br J Pharmacol. 2001;132(1):63-72. PubMed PMID: 11156562.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel mechanism of blocking axonal Na(+) channels by three macrocyclic polyamine analogues and two spider toxins. AU - Yakehiro,M, AU - Furukawa,Y, AU - Koike,T, AU - Kimura,E, AU - Nakajima,T, AU - Yamaoka,K, AU - Seyama,I, PY - 2001/1/13/pubmed PY - 2001/6/2/medline PY - 2001/1/13/entrez SP - 63 EP - 72 JF - British journal of pharmacology JO - Br J Pharmacol VL - 132 IS - 1 N2 - 1. The mechanism of Na(+) channel block by three macrocyclic polyamine derivatives and two spider toxins was studied with voltage clamp and internal perfusion method in squid axons. 2. All these chemicals specifically block Na(+) channels in the open state only from the internal surface, and do not affect K(+) channels. 3. The blocking effect is enhanced as the depolarizing pulse becomes larger. Blocked channels are unable to shift to the inactivated state. 4. In the case of cyclam and guanidyl-side armed cyclam (G-cyclam), quick release of these chemicals from the binding sites is proven by the increase in the tail current and prolongation of the time course of the off gating current. On the other hand, in the presence of N-4 and the spider toxins, their detachment was delayed significantly. 5. Molecular requirements for the block of Na(+) channels by these molecules are the presence of positive charge and hydrophobicity. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/11156562/Novel_mechanism_of_blocking_axonal_Na_+__channels_by_three_macrocyclic_polyamine_analogues_and_two_spider_toxins_ L2 - https://doi.org/10.1038/sj.bjp.0703765 DB - PRIME DP - Unbound Medicine ER -