This Article Full Text Full Text (PDF) Methods Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Baron, A. Articles by Baertschi, A. J. Search for Related Content PubMed PubMed Citation Articles by Baron, A. Articles by Baertschi, A. J. Related Collections Biochemistry and metabolism Ion channels/membrane transport Other Vascular biology

(Circulation Research. 1999;85:707-715.)
© 1999 American Heart Association, Inc.

Cellular Biology

A Novel K_ATP Current in Cultured Neonatal Rat Atrial Appendage Cardiomyocytes

Anne Baron, Laurianne van Bever, Dominique Monnier, Angela Roatti, Alex J. Baertschi

From the Department of Physiology, Centre Médical Universitaire, Geneva, Switzerland.

Correspondence to Alex J. Baertschi, Department of Physiology, Centre Médical Universitaire, 1 rue Michel Servet, CH-1211 Geneva 4, Switzerland. E-mail Alex.Baertschi{at}medecine.unige.ch

Abstract—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 H₂O or by the K⁺ channel openers diazoxide and cromakalim with EC₅₀ 1 and 10 nmol/L, respectively. The activated atrial K_ATP current was highly sensitive to glyburide, with an IC₅₀ 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 µmol/L diazoxide, and was inhibited by glyburide, with an IC₅₀ 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 ß-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.

Key Words: K_ATP channel • sulfonylurea receptor • cardiac atrium • atrial natriuretic peptide • patch clamp

This article has been cited by other articles:

				T. P. Flagg, H. T. Kurata, R. Masia, G. Caputa, M. A. Magnuson, D. J. Lefer, W. A. Coetzee, and C. G. Nichols Differential Structure of Atrial and Ventricular KATP: Atrial KATP Channels Require SUR1 Circ. Res., December 5, 2008; 103(12): 1458 - 1465. [Abstract] [Full Text] [PDF]

				A. Wheeler, C. Wang, K. Yang, K. Fang, K. Davis, A. M. Styer, U. Mirshahi, C. Moreau, J. Revilloud, M. Vivaudou, et al. Coassembly of Different Sulfonylurea Receptor Subtypes Extends the Phenotypic Diversity of ATP-sensitive Potassium (KATP) Channels Mol. Pharmacol., November 1, 2008; 74(5): 1333 - 1344. [Abstract] [Full Text] [PDF]

				J. W. Elrod, M. Harrell, T. P. Flagg, S. Gundewar, M. A. Magnuson, C. G. Nichols, W. A. Coetzee, and D. J. Lefer Role of Sulfonylurea Receptor Type 1 Subunits of ATP-Sensitive Potassium Channels in Myocardial Ischemia/Reperfusion Injury Circulation, March 18, 2008; 117(11): 1405 - 1413. [Abstract] [Full Text] [PDF]

				P. Philip-Couderc, N. I. Tavares, A. Roatti, R. Lerch, C. Montessuit, and A. J. Baertschi Forkhead Transcription Factors Coordinate Expression of Myocardial KATP Channel Subunits and Energy Metabolism Circ. Res., February 1, 2008; 102(2): e20 - e35. [Abstract] [Full Text] [PDF]

				K. W. Chan, A. Wheeler, and L. Csanady Sulfonylurea Receptors Type 1 and 2A Randomly Assemble to Form Heteromeric KATP Channels of Mixed Subunit Composition J. Gen. Physiol., December 31, 2007; 131(1): 43 - 58. [Abstract] [Full Text] [PDF]

				T. P. Flagg, B. Patton, R. Masia, C. Mansfield, A. N. Lopatin, K. A. Yamada, and C. G. Nichols Arrhythmia susceptibility and premature death in transgenic mice overexpressing both SUR1 and Kir6.2[{Delta}N30,K185Q] in the heart Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H836 - H845. [Abstract] [Full Text] [PDF]

				N. Saegusa, T. Sato, T. Saito, M. Tamagawa, I. Komuro, and H. Nakaya Kir6.2-deficient mice are susceptible to stimulated ANP secretion: KATP channel acts as a negative feedback mechanism? Cardiovasc Res, July 1, 2005; 67(1): 60 - 68. [Abstract] [Full Text] [PDF]

				L. van Bever, S. Poitry, C. Faure, R. I. Norman, A. Roatti, and A. J. Baertschi Pore loop-mutated rat KIR6.1 and KIR6.2 suppress KATP current in rat cardiomyocytes Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H850 - H859. [Abstract] [Full Text] [PDF]

				S. Poitry, L. van Bever, F. Coppex, A. Roatti, and A. J Baertschi Differential sensitivity of atrial and ventricular KATP channels to metabolic inhibition Cardiovasc Res, February 1, 2003; 57(2): 468 - 476. [Abstract] [Full Text] [PDF]

				P. Baumann, S. Poitry, A. Roatti, and A. J. Baertschi Plasmalemmal KATP channels shape triggered calcium transients in metabolically impaired rat atrial myocytes Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2296 - H2305. [Abstract] [Full Text] [PDF]

				A. Hambrock, R. Preisig-Muller, U. Russ, A. Piehl, P. J. Hanley, J. Ray, J. Daut, U. Quast, and C. Derst Four novel splice variants of sulfonylurea receptor 1 Am J Physiol Cell Physiol, August 1, 2002; 283(2): C587 - C598. [Abstract] [Full Text] [PDF]

				Y. Cui, S. Tran, A. Tinker, and L. H. Clapp The Molecular Composition of KATP Channels in Human Pulmonary Artery Smooth Muscle Cells and Their Modulation by Growth Am. J. Respir. Cell Mol. Biol., January 1, 2002; 26(1): 135 - 143. [Abstract] [Full Text] [PDF]

				A. Baron, D. Monnier, A. Roatti, and A. J. Baertschi Pituitary adenylate cyclase-activating polypeptide activates KATP current in rat atrial myocytes Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H1058 - H1065. [Abstract] [Full Text] [PDF]

				J. Seharaseyon, N. Sasaki, A. Ohler, T. Sato, H. Fraser, D. C. Johns, B. O'Rourke, and E. Marban Evidence against Functional Heteromultimerization of the KATP Channel Subunits Kir6.1 and Kir6.2 J. Biol. Chem., June 2, 2000; 275(23): 17561 - 17565. [Abstract] [Full Text] [PDF]

				J.-H. Jiao, P. Baumann, A. Baron, A. Roatti, R. A. Pence, and A. J. Baertschi Sulfonylurea receptor ligands modulate stretch-induced ANF secretion in rat atrial myocyte culture Am J Physiol Heart Circ Physiol, June 1, 2000; 278(6): H2028 - H2038. [Abstract] [Full Text] [PDF]

				A. P. Babenko and J. Bryan A Conserved Inhibitory and Differential Stimulatory Action of Nucleotides on KIR6.0/SUR Complexes Is Essential for Excitation-Metabolism Coupling by KATP Channels J. Biol. Chem., December 21, 2001; 276(52): 49083 - 49092. [Abstract] [Full Text] [PDF]