THE EFFECTS OF PIRACETAM AND ITS NOVEL PEPTIDE ANALOG 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 ne urons of the snail Helix pomatia: high threshold Ca2+ current (I-Ca), high-threshold Ca2+-dependent K+ current (I-K(Ca)) and high threshold K+ current independent of Ca2+ (I-K(V)). 2. The effect of bath applica tion of the nootropics piracetam and a novel piracetam peptide analog, ethyl ester of N-phenyl-acetyl-L prolyl glycine (GVS-111), on these t hree types of voltage activated ionic currents was studied. 3. In more than half of the tested cells, I-Ca was resistant to both piracetam a nd GVS-111. In the rest of the cells, Ic, decreased 19+/-7% with 2 mM of piracetam and 39+/-14% with 2 mu M of GVS-111. 4. I-K(V) in almost all cells tested was resistant to piracetam at concentrations up to 2 mM. However, I-K(V) in two-thirds of the cells was sensitive to GVS-11 1, being supressed 49+/-18% with 1 mu M GVS-111. 5. I-K(Ca) appeared t o be the most sensitive current of those studied to both piracetam and GVS-111. Piracetam at 1 mM and GVS-111 at 0.1 mu M decreased the ampl itude of I-K(Ca) in most of the cells examined by 49+/-19% and 69+/-24 %, respectively. 6. The results suggest that piracetam and GVS-111 sup pression of voltage-activated calcium and potassium currents of the ne uronal membrane may regulate (both up and down) Ca2+ influx into neuro ns. (C) 1997 Elsevier Science Inc.