The effects of piracetam and its novel peptide analogue GVS-111 on neuronal voltage-gated calcium and potassium channels.
1. With the use of the two-microelectrode voltage-clamp method, three types of voltage-activated ionic currents were examined in isolated neurons of the snail Helix pomatia: high-threshold Ca2+ current (ICa), high-threshold Ca(2+)-dependent K+ current (IK(Ca)) and high-threshold K+ current independent of Ca2+ (IK(V)). 2. The effect of bath application of the nootropics piracetam and a novel piracetam peptide analog, ethyl ester of N-phenyl-acetyl-L-prolyl-glycine (GVS-111), on these three types of voltage-activated ionic currents was studied. 3. In more than half of the tested cells, ICa was resistant to both piracetam and GVS-111. In the rest of the cells, ICa decreased 19 +/- 7% with 2 mM of piracetam and 39 +/- 14% with 2 microM of GVS-111. 4. IK(V) in almost all cells tested was resistant to piracetam at concentrations up to 2 mM. However, IK(V) in two-thirds of the cells was sensitive to GVS-111, being suppressed 49 +/- 18% with 1 microM GVS-111. 5. IK(Ca) appeared to be the most sensitive current of those studied to both piracetam and GVS-111. Piracetam at 1 mM and GVS-111 at 0.1 microM decreased the amplitude of IK(Ca) in most of the cells examined by 49 +/- 19% and 69 +/- 24%, respectively. 6. The results suggest that piracetam and GVS-111 suppression of voltage-activated calcium and potassium currents of the neuronal membrane may regulate (both up and down) Ca2+ influx into neurons.
Solntseva
E I
EI
Institute of Brain Research, Russian Academy of Medical Sciences, Moscow, Russia. Elena@synaptology.msk.su
Bukanova
J V
JV
Ostrovskaya
R U
RU
Gudasheva
T A
TA
Voronina
T A
TA
Skrebitsky
V G
VG
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D004151:Dipeptides / Q000494:pharmacology*; D006372:Helix, Snails; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018697:Nootropic Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010889:Piracetam / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*
D015220:Calcium Channels; D004151:Dipeptides; D018697:Nootropic Agents; D015221:Potassium Channels; C103871:ethyl phenylacetyl-Pro-Gly; D010889:Piracetam