Acetyl‐L‐Carnitine arginyl amide (ST857) increases calcium channel density in rat pheochromocytoma (PC12) cells

K. Tewari, J. Marc Simard, Y. B. Peng, K. Werrbach‐Perez, J. R. Perez‐Polo

    Research output: Contribution to journalArticle

    7 Scopus citations

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)371-378
    Number of pages8
    JournalJournal of Neuroscience Research
    Volume40
    Issue number3
    DOIs
    StatePublished - Feb 15 1995

    Keywords

    • Ca channel
    • PC12 cells
    • differentiation
    • nerve growth factor

    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience

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