Measurement of whole-cell calcium current in voltage-clamped vascular muscle cells

The direct measurement of transmembrane calcium current in single vascular muscle cells has been accomplished recently using the whole-cell voltage-clamp technique. The small size of the vascular muscle cell and the proportionately smaller magnitude of its inward calcium current necessitate refined instrumentation, but also make the vascular muscle cell an ideal candidate for whole-cell voltage-clamp recording. Calcium current in vascular muscle cells appears to have some, but not all, characteristics in common with calcium currents similarly isolated in neuronal and cardiac cells, including voltage-dependent activation and steady-state inactivation of calcium current, the presence of two current types, and sensitivity to inorganic and organic calcium channel modulating drugs. Future voltage-clamp analysis of calcium currents in vascular muscle is needed to further our understanding of the control of the calcium channels in physiological and pathophysiological states.     

EDC3 phosphorylation regulates growth and invasion through controlling P‐body formation and dynamics

Regulation of mRNA stability and translation plays a critical role in determining protein abundance within cells. Processing bodies (P‐bodies) are critical regulators of these processes. Here, we report that the Pim1 and 3 protein kinases bind to the P‐body protein enhancer of mRNA decapping 3 (EDC3) and phosphorylate EDC3 on serine (S)161, thereby modifying P‐body assembly. EDC3 phosphorylation is highly elevated in many tumor types, is reduced upon treatment of cells with kinase inhibitors, and blocks the localization of EDC3 to P‐bodies. Prostate cancer cells harboring an EDC3 S161A mutation show markedly decreased growth, migration, and invasion in tissue culture and in xenograft models. Consistent with these phenotypic changes, the expression of integrin β1 and α6 mRNA and protein is reduced in these mutated cells. These results demonstrate that EDC3 phosphorylation regulates multiple cancer‐relevant functions and suggest that modulation of P‐body activity may represent a new paradigm for cancer treatment.     

Sodium pump hyperpolarization-relaxation in rat caudal artery

Electrogenic ion transport contributes vitally to the Em in vascular muscle and thus is an important influence on contraction and relaxation. Agents that act on membrane ion transport will cause depolarization or hyperpolarization of sufficient magnitude to cause contraction or relaxation, respectively. In the caudal artery of the rat, the principal ion involved appears to be Na+. The transport process appears to be the Na+, K+-ATPase, which is ouabain sensitive, rather than other possible candidates such as the Na+-Ca2+ countertransport mechanism. The hyperpolarization and parallel relaxation found in caudal artery on return to K+ provide unequivocal evidence for an electrogenic Na+ pump. In contrast, the lack of a contraction on transition to O Na+ suggests that the caudal artery does not show an Na+-K+ countertransport system. Although other ion transport systems might be established later for caudal artery and other kinds of vascular muscle, it now appears that the electrogenic Na+ pump is the main ion transport system controlling contraction through a continuous contribution to Em.