Spider Polyamine Toxin

Abstract

In the early 1980s, a new type of polyamine toxins was found in the venom of several orb-web spiders. Joro spider toxins (JSTXs) in the venom of Nephila clavata and Nephila spider toxins (NSTXs) derived from Nephila maculata blocked postsynaptic glutamate receptors in the invertebrate and vertebrate nervous system. Subsequently, chemical characterization and synthesis of JSTXs and NSTXs were carried out. These toxins and a synthetic analog, 1-naphthylacetylated spermine (Naspm), effectively suppressed glutamate channel responses of AMPA/KA type in mammalian central neurons. By use of recombinant subunit receptors expressed in Xenopus oocytes, JSTX was found to cause subunit specific block of the Ca²⁺-permeable AMPA receptors. This specific nature of JSTX was utilized to identify Ca²⁺-permeable AMPA receptors in various neurons and glial cells. The JSTXs strongly suppressed excitatory postsynaptic currents (EPSCs) in the hippocampal CA1 neurons after transient brain ischemia. The results indicate that JSTXs are effective at blocking abnormal EPSCs that may induce Ca²⁺ accumulation leading to delayed neuronal death after transient ischemic insult. Recent evidence shows that Ca²⁺-permeable AMPA receptors are involved in a variety of nervous diseases including amyotrophic lateral sclerosis (ALS) and allodynia. The JSTXs are potentially useful to understand pathogenesis of these diseases.