KCNQ-encoded K⁺ channels (Kv7.x) define neuronal excitability and cardiac rhythmicity, however, there remains little information on Kv7 channels in the vasculature. In 2003, Ohya et al (2003) reported expression of KCNQ1 in murine portal vein (mPV) myocytes. Our subsequent study showed that the Kv7 selective blocker XE991 inhibited a sustained K⁺ current in mPV myocytes, depolarised the membrane potential and increased contractile activity (Yeung & Greenwood, 2005). The aim of the present study was to characterise further the impact of Kv7 channels in the mPV K⁺ current using retigabine, which activates Kv7.2–7.5 but not Kv7.1. Female BALB/c mice (6-8 weeks) were sacrificed by cervical dislocation and the portal vein excised. Cells were obtained by enzymatic dispersion for electrophysiological recordings and immunocytochemistry. Currents were recorded using the whole-cell voltage-clamp technique with an external solution of (mM): NaCl 126, KCl 5, MgCl₂ 1, CaCl₂ 0.1, glucose 11, HEPES 10, adjusted to pH 7.2 with NaOH. The internal solution contained (mM): KCl 130, MgCl₂ 1, ATP 2, HEPES 10, EGTA 5, adjusted to pH 7.2 with KOH. Currents were evoked by stepping to various test potential (V_T) from a holding potential (V_H) of –60 mV. Qualitative PCR of mPV tissue showed KCNQ1 and KCNQ4 gene expression. This was confirmed by antibody staining for Kv7.1 and Kv7.4 confined predominantly to the plasmalemmal region. In electrophysiological studies retigabine had bimodal effects on the mPV K⁺ current. At test potentials between –60 mV and –20 mV the peak K⁺ current was enhanced (20 µM increased current at V_T -20 mV by 46 ± 12 pA n=8). However at more depolarised V_T retigabine inhibited the outward current (eg 20 µM reduced the current at V_T +40 mV by 230 ± 36 pA, n=8). Inclusion of 4-AP (5 mM) was sufficient to ablate the inhibitory effect of retigabine yet still retain the current enhancement. Currents in the presence of 20 μM retigabine were inhibited by 10 μM XE991 (37 ± 5% at +40 mV, n=6). V½ of XE991-sensitive currents calculated from conductance-voltage plots was –7 ± 2 mV (k = 15 ± 1 mV, n=6). In contrast the V½ of XE991-sensitive currents with no pretreatment with retigabine was 1.7 ± 3.5 mV (n=4). In isometric tension recordings 20 μM retigabine reduced the amplitude (74 ± 4%, n=4) and increased the frequency (71 ± 9%, n=4) of inherent contractile responses. These data show that retigabine has pronounced effects on contractile activity and has bi-modal effects on membrane currents, which suggest that ion channels encoded by KCNQ4 have a significant impact in this vessel.