Serotonin depolarizes the membrane potential in rat mesenteric artery myocytes by decreasing voltage-gated K + currents

Abstract

We hypothesized that voltage-gated K + (K v) currents regulate the resting membrane potential ( E m), and that serotonin (5-HT) causes E m depolarization by reducing K v currents in rat mesenteric artery smooth muscle cells (MASMCs). The resting E m was about −40 mV in the nystatin-perforated patch configuration, and the inhibition of K v currents by 4-aminopyridine caused marked E m depolarization. The inhibition of Ca 2+-activated K + (K Ca) currents had no effect on E m. 5-HT (1 μM) depolarized E m by ∼11 mV and reduced the K v currents to ∼63% of the control at −20 mV. Similar 5-HT effects were observed with the conventional whole-cell configuration with a weak Ca 2+ buffer in the pipette solution, but not with a strong Ca 2+ buffer. In the presence of tetraethylammonium (1 mM), 5-HT caused E m depolarization similar to the control condition. These results indicate that the resting E m is largely under the regulation of K v currents in rat MASMCs, and that 5-HT depolarizes E m by reducing K v currents in a [Ca 2+] i-dependent manner.