A novel K(ATP) current in cultured neonatal rat atrial appendage cardiomyocytes.
The functional and pharmacological properties of ATP-sensitive K(+) (K(ATP)) channels were studied in primary cultured neonatal rat atrial appendage cardiomyocytes. Activation of a whole-cell inward rectifying K(+) current depended on the pipette ATP concentration and correlated with a membrane hyperpolarization close to the K(+) equilibrium potential. The K(ATP) current could be activated either spontaneously or by a hypotonic stretch of the membrane induced by lowering the osmolality of the bathing solution from 290 to 260 mOsm/kg H(2)O or by the K(+) channel openers diazoxide and cromakalim with EC(50) approximately 1 and 10 nmol/L, respectively. The activated atrial K(ATP) current was highly sensitive to glyburide, with an IC(50) of 1.22+/-0.15 nmol/L. Recorded in inside-out patches, the neonatal atrial K(ATP) channel displayed a conductance of 58.0+/-2.2 pS and opened in bursts of 133.8+/-20.4 ms duration, with an open time duration of 1.40+/-0.10 ms and a close time duration of 0.66+/-0.04 ms for negative potentials. The channel had a half-maximal open probability at 0.1 mmol/L ATP, was activated by 100 micromol/L diazoxide, and was inhibited by glyburide, with an IC(50) in the nanomolar range. Thus, pending further tests at low concentrations of K(ATP) channel openers, the single-channel data confirm the results obtained with whole-cell recordings. The neonatal atrial appendage K(ATP) channel thus shows a unique functional and pharmacological profile resembling the pancreatic beta-cell channel for its high affinity for glyburide and diazoxide and for its conductance, but also resembling the ventricular channel subtype for its high affinity for cromakalim, its burst duration, and its sensitivity to ATP. Reverse transcriptase-polymerase chain reaction experiments showed the expression of Kir6.1, Kir6.2, SUR1A, SUR1B, SUR2A, and SUR2B subunits, a finding supporting the hypothesis that the neonatal atrial K(ATP) channel corresponds to a novel heteromultimeric association of K(ATP) channel subunits.
Baron
A
A
Department of Physiology, Centre Médical Universitaire, Geneva, Switzerland.
van Bever
L
L
Monnier
D
D
Roatti
A
A
Baertschi
A J
AJ
D000255:Adenosine Triphosphate / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D020517:Atrial Appendage / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D019806:Cromakalim / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D004553:Electric Conductivity; D005905:Glyburide / Q000494:pharmacology; D007038:Hypotonic Solutions / Q000494:pharmacology; D010812:Physical Stimulation; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats
D007038:Hypotonic Solutions; D015221:Potassium Channels; D020033:Protein Isoforms; D019806:Cromakalim; D000255:Adenosine Triphosphate; D003981:Diazoxide; D005905:Glyburide