Significant circadian variations exist in the frequency of cardiac arrhythmia, but few studies have examined the relation between cardiac ion channels genes and biological clocks. We investigated this relation using suprachiasmatic nuclei lesion (SCNX) and pharmacological autonomic nervous system block (ANSB) mice. Significant 24-h variations were observed in the expression of clock genes Per2, Bmal1, and Dbp and ion channel genes KCNA5, KCND2, KCHIP2, and KCNK3 in the control mice hearts. In the SCNX mice, all genes examined lost circadian rhythm. In the ANSB mice, the expressions of the three clock genes were dampened significantly but still had circadian rhythm, whereas the four ion channel gene expressions lost rhythm. Heart rate also lost circadian rhythm in both the SCNX and ANSB mice. These results suggest that some ion channel gene expressions might be regulated by the central clock in the SCN through the ANS but not the peripheral clock in the heart.

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Astrocyte proliferation is strictly controlled during development and in the adult nervous system. In this study, we examined the role of sulfated hyaluronan (SHya) in the proliferation and differentiation of normal human astrocytes (NHAs). Cells were cultured with different concentrations of SHya for 7 days, and the number of viable cells and the presence of neural cell-specific genes were determined to assess their proliferation and development, respectively. With SHya, cell proliferation increased nonsignificantly. Furthermore, remarkable enhancing action by SHya on connexin-26, -32, and -43 gene expressions were observed during the culture of NHAs. It has been suggested that a fraction of NHAs have neural precursor activity that gives rise to astrocytes themselves, oligodendrocytes, and neurons. Our results clearly demonstrated that the expression of specific genes for neural precursor cells, astrocytes, neurons, and oligodendrocytes was significantly increased to 50 mug/mL in SHya-treated cultures when compared with that of the control culture. These findings suggest that SHya plays an important role in the proliferation and differentiation of NHAs and in the production of a novel material for tissue engineering.

The purpose of this study was to clarify the effect of hyaluronan (Hya) and sulfated hyaluronan (SHya) on rat calvarial osteoblast (rOB) cells proliferation and differentiation in vitro. rOB cells were cultured in the presence of Hya with different molecular weights (0.2, 2, 30, 90, 120 x 10 4) for 10days. Hya did not affect the proliferation of rOB cells. However, SHya suppressed the proliferation of rOB cells. The alkaline phosphatase (ALPase) activity of rOB cells cultured with SHya for 10 days was significantly enhanced in comparison with control (in the absence of polysaccharides) and with Hya. Hya suppressed the ALPase activity of rOB cells. As a result, SHya can control rOB cells proliferation and differentiation. SHya suppressed the rOB cells proliferation in a few culture days and promoted the differentiation. It was suggested that these effects were based on the sulfate groups of SHya. Therefore, it is considered that SHya is useful for the biomedical material, which promotes the differentiation of rOB cells.