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)