Effect of Aβ exposure on the mRNA expression patterns of voltage-sensitive calcium channel α1 subunits (α1A–α1D) in human SK-N-SH neuroblastoma

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Abstract

Evidence for loss of Ca2+ homeostasis through voltage-sensitive Ca2+ channels (VSCCs) contribution to neuronal degeneration induced by β-amyloid protein (Aβ) is considerable and rapidly increasing. Thus, the expression patterns of four α1 subunits for P/Q (α1A)-, N (α1B)-, and L (α1C and α1D)-type VSCCs before and after Aβ exposure were investigated in human SK-N-SH neuroblastoma. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed a constitutive and abundant co-expression of mRNA for α1A and α1D subunit in control cells. The mRNA expression of another L-type subunit α1C was undetectable in control cells while N-type subunit α1B was relative lower when compared to α1A and α1D subunits. Interestingly, mRNA levels of α1A, α1B, and α1C were remarkably and time-dependently increased in response to Aβ (20 μM) for 72 h culture period. In contrast, the constitutively expressed α1D mRNA was not further modified during Aβ exposure. Western blot analysis of four α1 subunits expression was consistent with the findings obtained by RT-PCR. In conclusion, our results suggested that P/Q-, N-, as well as L-type Ca2+ channel genes might be existed in SK-N-SH cells. Among them, mRNA for α1A, α1B, and α1D were expressed constitutively while α1C were inducible. Furthermore, Aβ exposure selectively modulates the transcription of α1A, α1B, and α1C subunits. These suggested that except activating of existed VSCCs, up-regulation of α1 subunits expression might also contribute to Aβ-induced neuronal toxicity and the complex of these VSCCs expression may participate in Ca2+ current disturbance in Alzheimer's disease.

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