Synthetic calpain activator boosts neuronal excitability without extra Ca2+.
Earlier we have shown that an equimolar mixture of calpastatin subdomains A and C (19 amino acids each) strongly activates m-calpain in vitro. In the present work we developed a membrane-permeable activator system, by conjugating an oligo-arginine tail to both peptides. We tested calpain activation as well as synaptic excitability on rat brain slices ex vivo. In hippocampal slices both basic excitability and long-term synaptic efficacy were significantly increased upon treatment with the activator. We propose that the activator peptide conjugates can be used with any mammalian cell, to specifically challenge the calpain system apparently without raising cytoplasmic Ca2+. Such an effector may be a useful tool in dissecting intracellular mechanisms involving the calpain system.
Világi
Ildikó
I
Department of Physiology and Neurobiology, Eötvös Loránd University, 1117 Budapest, Pázmány P. s. 1/C, Hungary.
Kiss
Dávid Sándor
DS
Farkas
Attila
A
Borbély
Sándor
S
Tárnok
Krisztián
K
Halasy
Katalin
K
Bánóczi
Zoltán
Z
Hudecz
Ferenc
F
Friedrich
Peter
P
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002522:Chlorocebus aethiops; D008297:Male; D008565:Membrane Proteins / Q000138:chemical synthesis* / Q000502:physiology*; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D055366:Synaptic Potentials / Q000187:drug effects / Q000502:physiology
D008565:Membrane Proteins; C410340:calpain activator; D002118:Calcium