Acetyl-L-carnitine arginyl amide (ST857) increases calcium channel density in rat pheochromocytoma (PC12) cells.
We used the patch clamp technique to study the effect of acetyl-L-carnitine arginyl amide (ALCAA) and of nerve growth factor (NGF) on availability of L-type Ca2+ channels in rat pheochromocytoma (PC12) cells maintained in defined medium. Channel availability was measured as number of channels in the patch x the probability of opening (n.Po). In patches from control cells, cells exposed to NGF (10 ng/ml) for six days, and cells exposed to ALCAA (1 mM) for six days, n.Po, measured during 200-240 ms pulses to -10 mV (holding potential, -60 mV), was 0.102 +/- 0.089 (5 cells), 0.173 +/- 0.083 (5 cells), and 0.443 +/- 0.261 (7 cells), respectively. The 4.3-fold increase for the ALCAA-treated cells was significantly different from control (P < 0.05), whereas that for the NGF-treated cells was not. For the same conditions, the maximum number of superimposed openings at -10 mV was 1.3 +/- 0.5 (6 cells), 1.6 +/- 0.5 (8 cells), and 3.3 +/- 1.8 (8 cells), with the value for the ALCAA-treated cells being significantly different from control (P < 0.001). Additional analysis showed that the distribution of channel open times, the time constants, and the voltage dependence of activation were not changed by prolonged exposure to ALCAA. Short-term exposure to both ALCAA as well as to the parent compound, acetyl-L-carnitine (ALCAR), did not cause an increase but rather a decrease in n.Po, and this short-term effect of both compounds was blocked by neomycin, an inhibitor of phospholipase C.(ABSTRACT TRUNCATED AT 250 WORDS)
Tewari
K
K
Division of Neurological Surgery, University of Maryland Medical System, Baltimore, USA.
Simard
J M
JM
Peng
Y B
YB
Werrbach-Perez
K
K
Perez-Polo
J R
JR
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D002331:Carnitine / Q000031:analogs & derivatives / Q000494:pharmacology*; D002478:Cells, Cultured; D005071:Evoked Potentials; D009355:Neomycin / Q000494:pharmacology; D016716:PC12 Cells / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats
D015220:Calcium Channels; D009355:Neomycin; D002331:Carnitine