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

K. Tewari, J. M. Simard, Y. B. Peng, K. Werrbach-Perez, J. R. Perez-Polo

Research output: Contribution to journalArticle

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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 x the probability of opening (n·P(o)). 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·P(o), 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·P(o), 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.

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

Fingerprint

Acetylcarnitine
PC12 Cells
Pheochromocytoma
Calcium Channels
Amides
Nerve Growth Factor
Neomycin
Type C Phospholipases
Patch-Clamp Techniques

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Acetyl-L-carnitine arginyl amide (ST857) increases calcium channel density in rat pheochromocytoma (PC12) cells. / Tewari, K.; Simard, J. M.; Peng, Y. B.; Werrbach-Perez, K.; Perez-Polo, J. R.

In: Journal of Neuroscience Research, Vol. 40, No. 3, 1995, p. 371-378.

Research output: Contribution to journalArticle

Tewari, K. ; Simard, J. M. ; Peng, Y. B. ; Werrbach-Perez, K. ; Perez-Polo, J. R. / Acetyl-L-carnitine arginyl amide (ST857) increases calcium channel density in rat pheochromocytoma (PC12) cells. In: Journal of Neuroscience Research. 1995 ; Vol. 40, No. 3. pp. 371-378.
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AU - Tewari, K.

AU - Simard, J. M.

AU - Peng, Y. B.

AU - Werrbach-Perez, K.

AU - Perez-Polo, J. R.

PY - 1995

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N2 - 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·P(o)). 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·P(o), 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·P(o), 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.

AB - 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·P(o)). 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·P(o), 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·P(o), 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.

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