INHIBITION OF VOLTAGE-ACTIVATED K-MUSCLE CELLS OF THE GUINEA-PIG PROXIMAL COLON BY NORADRENERGIC AGONISTS( CURRENTS IN SMOOTH)

1. The effects of noradrenaline and isoprenaline on the Ca-i(2+)-insen sitive, voltage-activated K+ current in smooth muscle cells from the c ircular muscle layer of the guinea pig proximal colon were investigate d by using standard whole-cell patch-clamp techniques at room temperat ure (22-24 degrees C). 2. The Ca2+-activated K+ current was eliminated by bathing cells in tetraethylammonium (TEA;2-5 mM) and a Ca2+ entry blocker (Cd2+, 0.1 mM) or nifedipine, 2-10 mu M) and by internally per fusing cells with 3 mM EGTA. 3. Two Ca2+-insensitive, voltage-activate d K+ currents were recorded at potentials positive to -50 mV: (a) a tr ansient 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 mu M) and isoprenaline ( 5-50 mu M) reduced the amplitudes of I-Kto and I-Kdet irreversibly aft er a slow onset (2-5 min). This reduction was mimicked by forskolin (5 0-100 mu M) and by 8 bromo-c AMP (500 mu M). 5. The voltage of half-ma ximal availability (V-0.5) of I-Kto (-74.6+/-2.3 mV) was unaffected by isoprenaline (10 mu M) (-76.7+/-3.6 mV, n=4), but the background ''le ak'' current (I-leak) was increased from -48+/-9 to -70+/-20 pA. 6. Ou r data suggest that stimulation of beta-adrenoceptors in the circular muscle layer of the guinea pig proximal colon inhibits voltage-activat ed Ca-i(2+)-insensitive K+ currents. (C) 1998 Elsevier Science Inc.