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Cardiac ATP-sensitive [K.sup.+] ([K.sub.ATP]) channels are formed by Kir6.2 and SUR2A subunits. We produced transgenic mice that express dominant negative Kir6.x pore-forming subunits (Kir6.1-AAA or Kir6.2-AAA) in cardiac myocytes by driving their expression with the [alpha]-myosin heavy chain promoter. Weight gain and development after birth of these mice were similar to nontransgenic mice, but an increased mortality was noted after the age of 4-5 mo. Transgenic mice lacked cardiac [K.sub.ATP] channel activity as assessed with patch clamp techniques. Consistent with a decreased current density observed at positive voltages, the action potential duration was increased in these mice. Some myocytes developed EADs after isoproterenol treatment. Hemodynamic measurements revealed no significant effects on ventricular function (apart from a slightly elevated heart rate), whereas in vivo electrophysiological recordings revealed a prolonged ventricular effective refractory period in transgenic mice. The transgenic mice tolerated stress less well as evident from treadmill stress tests. The proarrhythmogenic features and lack of adaptation to a stress response in transgenic mice suggest that these features are intrinsic to the myocardium and that [K.sub.ATP] channels in the myocardium have an important role in protecting the heart from lethal arrhythmias and adaptation to stress situations. potassium channels; ATP-sensitive [K.sup.+] channel; heart; ventricle; stress responses doi:10.1152/ajpheart.00051.2006

A study was conducted on the role of QLS motif in transmembrane helix VII of the glucose transporter family. The findings indicate that the QLS motif in helix VII functions as a molecular filter that dictates the ability of GLUTs 1, 3 and 4 to transport glucose. Moreover, this region of helix VII plays a key role in substrate recognition at the exofacial substrate binding site by interaction with the C-1 position of the incoming sugar molecule.

Alanine-scanning mutagenesis of putative transmembrane helix VIII and an investigation of the role of proline residues in transport catalysis were conducted to understand the structure-function of the brain-type glucose transporter, GLUT3. Results reveal that no individual amino acid within the helix is required for transport catalysis. Results also suggest that the role of the helix is to provide a framework for structural packing within the transporter molecule.

A range of chimeric glucose transporters composed of regions of liver-type (GLUT2) and brain-type (GLUT3) human facilitative glucose transporters were produced to determine the regions of the transporter which are involved in substrate recognition and binding. Findings indicate a model in which the seventh putative transmembrane-spanning helix is intimately involved in the selection of transported substrate and in which this region plays a critical role in determining the K(sub m) for 2-deoxyglucose.