The temporal and spatial regulation of intracellular calcium concentration ([Ca(2+)](i)) is very crucial for maintaining calcium ion homeostasis within cells, and consequently in the regulation of cellular functions such as beta cell replication and differentiation, insulin secretion, and apoptosis. Calcium ion regulatory proteins playing major roles in these processes include L-type voltage-dependent calcium channels (L-type VDCCs) and calcium-sensing receptors (CaRs). Tumor necrosis factor alpha (TNF-alpha), a cytokine, is widely known to activate nuclear factor-kappa B (NF-kappaB) transcription in beta cells. Confocal fluorescence imaging data suggest increased co-localization of CaRs with L-type VDCCs upon treatment of beta cells with TNF-alpha, thereby indicating increased membrane-delimited spatial interactions between these two membrane proteins.
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