title: Identification and properties of an ATP-sensitive K+ current in rabbit sino-atrial node pacemaker cells.
abstract: 1. Single myocytes were isolated from rabbit sino-atrial (SA) node by enzymatic dissociation. Spontaneous pacemaker activity, whole-cell and single-channel currents were recorded under conditions known to modulate ATP-sensitive K+ (KATP) channels. 2. The KATP channel openers, cromakalim and pinacidil, slowed or abolished the pacemaker activity, and caused hyperpolarization of the maximum diastolic potential (MDP). Glibenclamide, a KATP channel blocker, reversed these effects. Cromakalim- and pinacidil-activated currents reversed near the potassium equilibrium potential, EK. Glibenclamide had no effect on the L-type calcium current, ICa(L), the hyperpolarization-activated inward current, If, or the delayed rectifier potassium current, IK. 3. Sodium cyanide, which inhibits mitochondrial ATP production, induced a macroscopic current that reversed near EK and was blocked by glibenclamide. 4. In excised, inside-out patches from SA node cells, single KATP channels showed a slope conductance of 52 +/- 8 pS (mean +/- S.D.) when measurements were made at negative voltages in symmetric, 140 mM K+. Channels from ventricular myocytes showed a somewhat larger slope conductance (70 +/- 5 pS). 5. Raising the intracellular ATP concentration caused a concentration-dependent reduction in the open probability of the KATP channels (IC50, 16 microM; Hill coefficient, approximately 1; at both pH 7.4 and 6.8). 6. In excised inside-out patches, cromakalim or pinacidil induced significant increases in KATP channel activity in the presence of 50 microM or 1 mM intracellular ATP. This channel activity was blocked by glibenclamide. 7. Our results suggest that sino-atrial node cells express a distinct isoform of KATP channel which may play an important role in pharmacological and pathophysiological modulation of pacemaker activity.
authors.affiliation: Department of Medical Physiology, University of Calgary, Alberta, Canada.
authors.forename: X
authors.initials: X
authors.lastname: Han
authors.forename: P E
authors.initials: PE
authors.lastname: Light
authors.forename: W R
authors.initials: WR
authors.lastname: Giles
authors.forename: R J
authors.initials: RJ
authors.lastname: French
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D005905:Glyburide / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism; D018408:Patch-Clamp Techniques; D020110:Pinacidil; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology / Q000378:metabolism*; D012966:Sodium Cyanide / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001578:Benzopyrans; D006146:Guanidines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D020110:Pinacidil; D000255:Adenosine Triphosphate; D012966:Sodium Cyanide; D011188:Potassium; D005905:Glyburide