The overall interest of our laboratory is the regulation of skeletal muscle contraction, with an emphasis on the respiratory neuromuscular system. Current areas of focus are the regulation of diaphragm muscle contraction by K+ channels, and the control of acetylcholine release and replenishment at the phrenic-diaphragm neuromuscular junction, as described further below. Other areas of investigation include the contractile and structural properties of thoracic and upper airway respiratory muscles, and the manner in which their activity is controlled by the brain during breathing.

Skeletal muscles contain a high density of membranous K+ channels, including voltage-senstive delayed and inward rectifier K+ channels, Ca++-activated K+ channels, and ATP-sensitive K+ channels. Studies are examining the extent to which alteration of K+ conductance through one or more of these channels alters muscle contractile performance. In particular, the role of delayed rectifier channels are being defined, as these are the channels responsible for action potential repolarization. Studies are finding that K+ channel blockade augments muscle force at low to intermediate stimulation frequencies, and that the force increases can be maintained over time during repetitive stimulation. Moreover, the magnitude of the force increases exceeds that typically seen with other skeletal muscle inotropic agents. The extent to which the salutatory effects of K+ channel blockers on muscle contractile performance extend to diseased muscle is being tested, which may lead to the development of a new therapeutic approach to a variety of muscle disorders.

Transmission at the neuromuscular junction requires sufficient acetylcholine release so that the consequentially elicited postsynaptic endplate potential exceeds the threshold for action potential generation. During repetitive activation, transmitter release diminishes, which when severe leads to transmission failure. This issue is particularly important for respiratory neuromuscular junctions, which unlike limb neuromuscular junctions remain active throughout the lifetime of the organism. Restoration of acetylcholine available for release depends on two separate but interrelated processes: recycling of transmitter from the synaptic cleft, and repletion of the immediately releaseable vesicle pool from one or more reserve pools. Respiratory muscles are active continuously, so that transmitter replenishment needs to be sufficiently robust to ensure that a constant supply of acetylcholine is available for release. Studies are defining intrinsic and extrinsic factors which regulate neurotransmitter replenishment, in particular stimulation frequency, intracellular Ca++ levels, temperature and hypoxia.

1. van Lunteren E, Moyer M, Leahy P. (2006)
   Gene expression profiling of diaphragm muscle in alpha2-laminin (merosin)-deficient dy/dy dystrophic mice. Physiol Genomics. 2006 Mar 13; 25(1):85-95. 2005/12/20 [aheadofprint].
   
2. van Lunteren E, Moyer M. (2005)
   Altered diaphragm muscle action potentials in zucker diabetic fatty (ZDF) rats. Respir Physiol Neurobiol. 2005 Nov 24;
   
3. van Lunteren E, Moyer M. (2005)
   Modulation of biphasic rate of end-plate potential recovery in rat diaphragm. Muscle Nerve. 2005 Mar; 31(3):321-330.
   
4. van Lunteren E, Moyer M, Pollarine J. (2004)
   Reduced amount and disrupted temporal pattern of spontaneous exercise in diabetic rats. Med Sci Sports Exerc. 2004 Nov; 36(11):1856-1862.
   
5. van Lunteren E, Moyer M. (2004)
   Combination of variable frequency train stimulation and K+ channel blockade to augment skeletal muscle force. IEEE Trans Neural Syst Rehabil Eng. 2004 Jun; 12(2):288-294.
   
6. van Lunteren E, Moyer M, Kaminski HJ. (2004)
   Adverse effects of myasthenia gravis on rat phrenic diaphragm contractile performance. J Appl Physiol. 2004 Sep; 97(3):895-901. 2004/04/23 [aheadofprint].
   
7. van Lunteren E, Moyer M. (2003)
   Reduced fatigue in diaphragm muscle of merosin-deficient DY/DY dystrophic mice. Respiration. 2003 Nov-Dec; 70(6):636-642.
   
8. van Lunteren E, Moyer M. (2003)
   Streptozotocin-diabetes alters action potentials in rat diaphragm. Respir Physiol Neurobiol. 2003 Apr 15; 135(1):9-16.
   
9. Van Lunteren E, Moyer M. (2003)
   Wheel-running exercise alters rat diaphragm action potentials and their regulation by K+ channels. J Appl Physiol. 2003 Aug; 95(2):602-610. 2003/04/18 [aheadofprint].
   
10. van Lunteren E, Moyer M. (2003)
    Slowing of rat diaphragm action potential depolarization by endurance treadmill training. Neurosci Lett. 2003 Mar 27; 339(3):175-178.
    
11. van Lunteren E, Sankey C, Moyer M, Snajdar RM. (2002)
    Role of K+ channels in L-6 myoblast migration. J Muscle Res Cell Motil. 2002; 23(3):197-204.
    
12. Van Lunteren E, Kaminski HJ. (1999)
    Disorders of Sleep and Breathing during Sleep in Neuromuscular Disease. Sleep Breath. 1999; 3(1):23-30.
    
13. van Lunteren E, Moyer M. (2001)
    Auxotonic contractile responses of rat tracheal and bronchial airway smooth muscle. Pulm Pharmacol Ther. 2001; 14(6):443-453.
    
14. Moyer M, van Lunteren E. (2001)
    Effect of temperature on endplate potential rundown and recovery in rat diaphragm. J Neurophysiol. 2001 May; 85(5):2070-2075.
    
15. van Lunteren E, Manubay P. (2001)
    Inotrophic effects of the K(+) channel blocker TEA on dystrophic (mdx and dy/dy) mouse diaphragm. Respir Physiol. 2001 Apr; 125(3):249-254.
    
16. van Lunteren E, Dick TE. (2001)
    Heterogeneity within geniohyoid motor unit subpopulations in firing patterns during breathing. Respir Physiol. 2001; 124(1):23-33.
    
17. Manubay P, van Lunteren E. (2000)
    Effects on dystrophic (dy/dy) limb muscle of the K+ channel blocker tetraethylammonium. Neurosci Lett. 2000 Apr 14; 283(3):169-172.
    
18. van Lunteren E, Sankey CB. (2000)
    Catchlike property of rat diaphragm: subsequent train frequency effects in variable-train stimulation. J Appl Physiol. 2000 Feb; 88(2):586-598.
    
19. Moyer M, van Lunteren E. (1999)
    Effect of phasic activation on endplate potential in rat diaphragm. J Neurophysiol. 1999 Dec; 82(6):3030-3040.
    
20. van Lunteren E, Snajdar RM. (1999)
    Attenuation of rat diaphragm low-frequency fatigue by vanadate in vitro. Respir Physiol. 1999 Sep 15; 117(2-3):121-130.
    
21. van Lunteren E, Moyer M. (1999)
    Peptide toxin blockers of voltage-sensitive K+ channels: inotropic effects on diaphragm. J Appl Physiol. 1999 Mar; 86(3):1009-1016.
    
22. van LUNTEREN E, Moyer M. (1998)
    Electrophysiologic and inotropic effects of K+-channel blockade in aged diaphragm. Am J Respir Crit Care Med. 1998 Sep; 158(3):820-826.
    
23. Van Lunteren E, Moyer M, Torres A. (1998)
    ATP-sensitive K+ channel blocker glibenclamide and diaphragm fatigue during normoxia and hypoxia. J Appl Physiol. 1998 Aug; 85(2):601-608.