Transient outward K+ current density varies during the cell cycle in GH3 pituitary cells and its blockade inhibits cell proliferation, suggesting a role in proliferation processes.
I(to) reduction in S-phase cells is hypothesis-generating for proliferation links in pituitary models; leaves open extension to cardiac myocytes.
Our aim was to determine whether the expression of K(+) currents is related to the cell cycle in the excitable GH3 pituitary cell line. K(+) currents were studied by electrophysiology, and bromodeoxyuridine (BrdU) labeling was used to compare their expression in cells thereafter identified as being in the S or non-S phase of the cell cycle. We show that the peak density of the transient outward K(+) current (I(to)) was 33% lower in cells in S phase (BrdU+) than in cells in other phases of the cell cycle (BrdU-). The voltage-dependence of I(to) was not modified. However, of the two kinetic components of I(to) inactivation, the characteristics of the fast component differed significantly between BrdU+ and BrdU- cells. Recovery from inactivation of I(to) showed biexponential and monoexponential function in BrdU- and BrdU+ cells, respectively. This suggests that the molecular basis of this current varies during the cell cycle. We further demonstrated that 4-aminopyridine, which blocks I(to), inhibited GH3 cell proliferation without altering the membrane potential. These data suggest that I(to) may play a role in GH3 cell proliferation processes.
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Czarnecki et al. (2000) studied this question.
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