Molecular determinants of two neurotoxins that regulate sodium current inactivation in rat hippocampal neurons.
We studied functional and structural differences between the two neurotoxins, wasp toxin pompilidotoxin (PMTX) and sea anemone toxin (ATXII). Although PMTX and ATXII inhibited inactivation of sodium currents both toxins had distinct actions on the lobster axon and on the rat hippocampal cells. To determine structural basis of the difference we compared arrangement of polar and non-polar amino acids of the two toxins and found that similar sequence of PMTX exist in a discrete position of three-dimensional structure of ATXII. The sequence may be responsible for the binding site in the neuronal Na(+) channel molecule because PMTX is insensitive to cardiac Na(+) channel. Differential actions of ATXII from PMTX may come from other regions than the overlapped sequence. PMTX has diverse actions in the central neurons and is useful to classify Na(+) channel subtypes.
Kawai
Nobufumi
N
Department of Physiology, Jichi Medical School, Minamikawachi-machi, Tochigi-ken 329-0498, Japan. kawainob@jichi.ac.jp
Konno
Katsuhiro
K
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003064:Cnidarian Venoms / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D019476:Insect Proteins; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D008121:Nephropidae; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000737:chemistry / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000145:classification / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014862:Wasp Venoms
D003064:Cnidarian Venoms; D019476:Insect Proteins; D009498:Neurotoxins; D015222:Sodium Channels; D014862:Wasp Venoms; C115328:pompilidotoxin alpha; C028800:toxin II (Anemonia sulcata); D012964:Sodium