Inhibition of Voltage-Activated K + Currents in Smooth Muscle Cells of the Guinea Pig Proximal Colon by Noradrenergic Agonists

Abstract

1. The effects of noradrenaline and isoprenaline on the Ca 2+ i-insensitive, voltage-activated K + current in smooth muscle cells from the circular muscle layer of the guinea pig proximal colon were investigated by using standard whole-cell patch-clamp techniques at room temperature (22–24°C). 2. The Ca 2+-activated K + current was eliminated by bathing cells in tetraethylammonium (TEA;2–5 mM) and a Ca 2+-entry blocker (Cd 2+, 0.1 mM) or nifedipine, 2–10 μM) and by internally perfusing cells with 3 mM EGTA. 3. Two Ca 2+ i-insensitive, voltage-activated K + currents were recorded at potentials positive to −50 mV: (a) a transient K + current ( I Kto) that was blocked by 4-aminopyridine (5 mM) and (b) a delayed rectifier-type K + current ( I Kdel) that was blocked by TEA (>10 mM). 4. Both noradrenaline (10–50 μM) and isoprenaline (5–50 μM) reduced the amplitudes of I Kto and I Kdel irreversibly after a slow onset (2–5 min). This reduction was mimicked by forskolin (50–100 μM) and by 8 bromo-c-AMP (500 μM). 5. The voltage of half-maximal availability ( V 0.5) of I Kto (−74.6±2.3 mV) was unaffected by isoprenaline (10 μM) (−76.7±3.6 mV, n=4), but the background “leak” current ( I leak) was increased from −48±9 to −70±20 pA. 6. Our data suggest that stimulation of β-adrenoceptors in the circular muscle layer of the guinea pig proximal colon inhibits voltage-activated Ca 2+ i-insensitive K + currents.