John H. Caldwell Professor Cell and Developmental Biology / Physiology and Biophysics Ph.D., Washington University, 1977 UCHSC at Fitzsimons RC-1 North, Room 7105 PO Box 6511, Mail Stop 8108 Aurora, CO 80045 Phone: 303-724-3190 Fax: 303-724-3420 Email: John.Caldwell@uchsc.edu

Ion Channels

Ion channels are essential for the regulation of every cellular function, whether it is the beating of the heart or the storing of memories. The focus of the laboratory is upon ion channels in two areas, the Golgi apparatus and the nervous system. Ion channels in these areas are being studied using a variety of techniques, including molecular biology and electrophysiology.

The Golgi apparatus is an intracellular organelle that is in every eucaryotic cell, from yeast to humans. It is important for modifying proteins and targeting them to the correct location in the cell. Although ion channels have been isolated and characterized from virtually every other intracellular organelle, no channels endogenous to the Golgi have been described. In collaboration with Dr. Howell's laboratory, we have isolated ion channels from the Golgi and incorporated these channels into planar lipid bilayers to study their electrical properties. We have found an anion channel with novel properties. For example, it is modulated by pH and may be important for establishing the low pH inside the Golgi. Future studies are aimed at isolating cDNA and determining the functional role. We predict that this channel will be expressed ubiquitously.

Electrical signaling in the nervous system relies on the correct activation and inactivation of ion channels. We have recently cloned a new voltage-gated sodium channel (NaCh6) that is expressed in neurons of the central and peripheral nervous systems. We have generated antibodies that are specific to this channel and have used these to show that the channel is in both the presynaptic axon and the postsynaptic dendrite. Mice with natural mutations in this channel have been identified, and these mice have neurological disorders that involve motor neurons and the cerebellum. We expect that some human neurological disorders are due to mutations in NaCh6, and studies of these mice will help identify and understand the cause of these disorders.

Selected Publications

Thompson RJ, Nordeen MH, Howell KE, Caldwell JH. A large-conductance anion channel of the Golgi complex. Biophys J. 2002 Jul;83(1):278-89.

Boiko T, Rasband MN, Levinson SR, Caldwell JH, Mandel G, Trimmer JS, Matthews G. Compact myelin dictates the differential targeting of two sodium channel isoforms in the same axon. Neuron. 2001 Apr;30(1):91-104.

Goldin AL, Barchi RL, Caldwell JH, Hofmann F, Howe JR, Hunter JC, Kallen RG, Mandel G, Meisler MH, Netter YB, Noda M, Tamkun MM, Waxman SG, Wood JN, Catterall WA. Nomenclature of voltage-gated sodium channels. Neuron. 2000 Nov;28(2):365-8.

Nordeen MH, Jones SM, Howell KE, Caldwell JH. GOLAC: an endogenous anion channel of the Golgi complex. Biophys J. 2000 Jun;78(6):2918-28.

Caldwell JH, Schaller KL, Lasher RS, Peles E, Levinson SR. Sodium channel Na(v)1.6 is localized at nodes of ranvier, dendrites, and synapses. Proc Natl Acad Sci U S A. 2000 May 9;97(10):5616-20.

Latest Publications in PubMed