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 × the probability of opening (n^.P₀). 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^.P₀, 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^.P₀, and this short-term effect of both compounds was blocked by neomycin, an inhibitor of phospholipase C. Together, our findings are consistent with the interpretation that short-term exposure to ALCAA inhibits Ca²⁺ channel activity, possibly by increasing intracellular Ca²⁺, and that long-term exposure causes an increase in Ca²⁺ channel density, possibly by increasing channel expression, with no change in Ca²⁺ channel properties. © 1995 Wiley-Liss, Inc.