page_title: Kalkitoxin
section_title: Mode of action
hierarchical_section_title: Kalkitoxin / Mode of action
caption_attribution_description: English: This figure illustrates the two distinct interactions kalkitoxin makes with receptors in the glutamatergic synapse, and how these two interactions are oppositional at the level of neuronal survival.
context_page_description: Kalkitoxin, a toxin derived from the cyanobacterium Lyngbya majuscula, induces NMDA receptor mediated neuronal necrosis, blocks voltage-dependent sodium channels, and induces cellular hypoxia by inhibiting the electron transport chain complex 1.
context_section_description: Kalkitoxin induces delayed neuronal necrosis in cerebellar granule cells of the rat. This neuronal necrosis proved to be NMDA-receptor mediated. These receptors are normally activated by glutamate and other excitotoxic compounds and can induce neuronal necrosis. It is not yet known if the toxin induces necrosis directly or via the release of excitotoxic compounds.
  Secondly, kalkitoxin blocks voltage-gated sodium channels, thereby inhibiting Ca²⁺ release that normally occurs when the voltage-gated sodium channel is activated, in a concentration dependent matter. Calcium release has been shown to induce lactate dehydrogenase (LDH) production. The amount of LDH is a measure for neuronal cell death. In the presence of kalkitoxin there is also a concentration-dependent inhibition of neuronal cell death and LDH production (9). The mechanism behind this inhibition is still unknown.
  Thirdly, kalkitoxin blocks the electron transport chain (ETC) complex 1, one of the protein complexes  involved in mitochondrial respiration. By blocking the ETC complex 1, kalkitoxin potently inhibits hypoxia-inducible factor-1 (HIF-1) activation. HIF-1 is a transcription factor, which enhances the expression of genes that increase oxygen availability, as well as genes that decrease oxygen consumption. Inhibition of HIF-1, which is one of the main effects of kalkitoxin, thus induces cellular hypoxia.
caption: This figure illustrates the two distinct interactions kalkitoxin makes with receptors in the glutamatergic synapse, and how these two interactions are oppositional at the level of neuronal survival.
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