CA2-SUBUNIT TRANSCRIPTS ARE DIFFERENTIALLY EXPRESSED IN RAT PHEOCHROMOCYTOMA (PC12) CELLS FOLLOWING NERVE GROWTH-FACTOR TREATMENT( CHANNEL ALPHA(1))

In this report, we describe the effect of nerve growth factor (SCF) on the transcriptional expression of voltage-dependent Ca2+ channel alph a(1) subunits, i.e., alpha(1A), alpha(1B), alpha(1C), alpha(1D), and a lpha(1E) in rat pheochromocytoma (PC12) cells. Using reverse transcrip tase-coupled polymerase chain reaction (RT-PCR) and class-specific Ca2 + channel oligonucleotide probes, messenger RNA levels were measured a nd compared to Histone H3.3 transcript which remained relatively const ant over the duration of NGF treatment. Although no statistically sign ificant differences in P-type (alpha(1A)) Ca2+ channel transcript leve ls were observed, N-type (alpha(1B)) Ca2+ channel transcript levels in creased 50% over control values (P values < 0.05) at days 7 and 14. In contrast, NGF treatment resulted in decreased levels of L-type (alpha (1C) and alpha(1D)) transcripts with alpha(1C) decreasing steadily to similar to 50% of control (P value < 0.01) by 2 weeks, while alpha(1D) decreased to similar to 20% of control (P value < 0.01) after 2 days treatment, No alpha(1E) Ca2+ channel transcripts were detected in PC12 cells, For comparison, PC12 cells were also treated with another diff erentiative growth factor, i.e., basic fibroblast growth factor (bFGF) and a nondifferentiative growth factor epidermal growth factor (EGF). In contrast to NGF, bFGF and EGF treatment had no inhibitory effect o n L-type (alpha(1C) and alpha(1D)) channel transcript levels after 3 d ays, Like NGF, EGF treatment had no statistically significant effect u pon P-type (alpha(1A)) transcript levels but increased in a biphasic m anner following bFGF treatment. Presynaptic-associated alpha(1B) (N-ty pe) Ca2+ channel transcripts were observed decreased following EGF tre atment (2 days) while L-type alpha(1C) transcripts decreased after 7 d ays (P value < 0.01). Although a varied response to differentiative gr owth Factors NGF and bFGF was observed, data presented here indicate t hat NGF treatment of PC12 cells results in 'late' increased expression of N-type Ca2+ channel transcripts, while L-type (alpha(1C) and alpha (1D)) Ca2+ channel transcripts appear to be down regulated. (C) 1998 I SDN, Published by Elsevier Science Ltd.