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.