Excitability of cells and tissues is an essential physiological function that allows organisms to sense their environment and respond to it. The primary goal of this work is to explain key physical-chemical features of cell and tissue excitability, many aspects of which are still poorly understood. Widely accepted theories of nerve excitability fail to explain several anomalous phenomena that we have observed, which we have shown are also necessary for excitation to occur. These include volume and temperature changes of the superficial protoplasmic layer of nerve axons, which coincide with the action potential waveform. We have obtained further evidence that these changes accompany a phase transition that occurs in nerve cells, fibers, and synapses caused by the exchange of divalent cations like calcium with monovalent cations like sodium and potassium. Our previous experiments with perfused axons clearly implicate divalent/monovalent cation exchange as a mechanism by which nerve fibers can be excited in an """"""""all or none"""""""" manner. To understand the physical chemical basis of these temperature and volumetric changes, particularly how divalent/monovalent cation exchange can induce such changes in biomolecular assemblies, we are studying these processes in synthetic """"""""biomimetic"""""""" anionic polymer gels under nearly physiological conditions. An advantage of studying the behavior of these gel model systems is that their structure, composition, and the interactions among its components can be carefully controlled, unlike living tissue. In particular, in synthetic polyacrylate gels, Ferenc Horkay has observed that minute changes in the concentration of divalent cations in the surrounding liquid can induce significant changes in chain stiffness in the gel, even if ion binding is weak and completely reversible. Various physical chemical and polymer physics-based techniques, including neutron scattering, osmotic swelling, and mechanical loading provide complementary information with which to study these biologically relevant phenomena over a wide range of length scales. These basic studies are leading to a deeper understanding of the physical mechanisms underlying nerve excitation.

Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2002
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Indirect Cost
Name
U.S. National Inst/Child Hlth/Human Dev
Department
Type
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Country
United States
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Miranda, P C; Correia, L; Salvador, R et al. (2007) Tissue heterogeneity as a mechanism for localized neural stimulation by applied electric fields. Phys Med Biol 52:5603-17
Silva, Sofia; Basser, Peter J; Miranda, Pedro C (2007) The activation function of TMS on a finite element model of a cortical sulcus. Conf Proc IEEE Eng Med Biol Soc 2007:6657-60
Miranda, Pedro C; Correia, Ludovic; Salvador, Ricardo et al. (2007) The role of tissue heterogeneity in neural stimulation by applied electric fields. Conf Proc IEEE Eng Med Biol Soc 2007:1715-8
Tasaki, Ichiji (2006) A note on the local current associated with the rising phase of a propagating impulse in nonmyelinated nerve fibers. Bull Math Biol 68:483-90
Tasaki, Ichiji (2005) Repetitive abrupt structural changes in polyanionic gels: a comparison with analogous processes in nerve fibers. J Theor Biol 236:2-11
Tasaki, Ichiji (2004) On the conduction velocity of nonmyelinated nerve fibers. J Integr Neurosci 3:115-24
Basser, Peter J (2004) Scaling laws for myelinated axons derived from an electrotonic core-conductor model. J Integr Neurosci 3:227-44
Miranda, Pedro C; Hallett, Mark; Basser, Peter J (2003) The electric field induced in the brain by magnetic stimulation: a 3-D finite-element analysis of the effect of tissue heterogeneity and anisotropy. IEEE Trans Biomed Eng 50:1074-85
Tasaki, Ichiji (2002) Spread of discrete structural changes in synthetic polyanionic gel: a model of propagation of a nerve impulse. J Theor Biol 218:497-505
Tasaki, Ichiji; Matsumoto, Gen (2002) On the cable theory of nerve conduction. Bull Math Biol 64:1069-82

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