Properties of the ATP-sensitive K+ current activated by levcromakalim in isolated pulmonary arterial myocytes.
Tension and patch clamp recording techniques were used to investigate the relaxation of rabbit pulmonary artery and the properties of the K+ current activated by levcromakalim in isolated myocytes. Under whole-cell voltage clamp, holding at -60 mV in symmetrical 139 mM K+, levcromakalim (10 microM) induced a noisy inward current of -116 +/- 19 pA (n = 13) which developed over 1 to 2 min. This current could be blocked by either glibenclamide (10 microM) or phencyclidine (5-50 microM) and was unaffected when extracellular Ca2+ was removed. Both these drugs inhibited the levcromakalim-induced relaxation of muscle strips precontracted with 20 mM [K+]o. Application of voltage ramps in symmetrical 139 mM K+ confirmed that the levcromakalim-induced current was carried by K+ ions and was weakly voltage dependent over the potential range from -100 to +40 mV. The unitary current amplitude and density of the channels underlying the levcromakalim-activated whole-cell K+ current was estimated from the noise in the current record. We estimate that levcromakalim caused activation of around 300 channels per cell, with a single channel current of 1.1 pA, corresponding to a slope conductance of about 19 pS. Furthermore, cells dialyzed with an ATP-free pipette solution developed a large noisy inward current at -60 mV, which could subsequently be blocked by flash photolysis of caged ATP. Analysis of the noise associated with this current indicated that the single channel amplitude underlying the ATP-blocked current was 1.4 pA, a value similar to that estimated for the levcromakalim-induced current.(ABSTRACT TRUNCATED AT 250 WORDS)
Clapp
L H
LH
Cardiovascular Research, Rayne Institute, St Thomas's Hospital, London, United Kingdom.
Gurney
A M
AM
Standen
N B
NB
Langton
P D
PD
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002469:Cell Separation; D019806:Cromakalim; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010622:Phencyclidine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011651:Pulmonary Artery / Q000166:cytology / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D000255:Adenosine Triphosphate; D010622:Phencyclidine