Inhibition of voltage-activated K+ currents in smooth muscle cells of the guinea pig proximal colon by noradrenergic agonists.
1. The effects of noradrenaline and isoprenaline on the Ca2+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 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 microM) and by internally perfusing cells with 3 mM EGTA. 3. Two Ca2+i-insensitive, voltage-activated K+ currents were recorded at potentials positive to -50 mV: (a) a transient K+ current (IKto) that was blocked by 4-aminopyridine (5 mM) and (b) a delayed rectifier-type K+ current (IKdel) that was blocked by TEA (>10 mM). 4. Both noradrenaline (10-50 microM) and isoprenaline (5-50 microM) reduced the amplitudes of IKto and IKdel irreversibly after a slow onset (2-5 min). This reduction was mimicked by forskolin (50-100 microM) and by 8 bromo-c-AMP (500 microM). 5. The voltage of half-maximal availability (V0.5) of IKto (-74.6+/-2.3 mV) was unaffected by isoprenaline (10 microM) (-76.7+/-3.6 mV, n=4), but the background "leak" current (Ileak) was increased from -48+/-9 to -70+/-20 pA. 6. Our data suggest that stimulation of beta-adrenoceptors in the circular muscle layer of the guinea pig proximal colon inhibits voltage-activated Ca2+i-insensitive K+ currents.
Department of Physiology, Monash University, Clayton, Victoria, Australia. fvogalis@warren.med.harvard.edu
F
F
Vogalis
R J
RJ
Lang
R A
RA
Bywater
G S
GS
Taylor
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000322:Adrenergic Agonists / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D003106:Colon / Q000166:cytology / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*
D000322:Adrenergic Agonists; D015220:Calcium Channels; D015221:Potassium Channels; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D007545:Isoproterenol