This application proposes to examine the characteristics and functional significance of sodium-activated potassium channels (IK(Na)) in vertebrate central and peripheral neurons. Preliminary results indicate that this current plays a major role in determining the voltage-dependent electrical behavior of cells where it is present. The experiments described below will examine the following questions: First, what are the kinetic properties of IK(Na), and are these determined by the time course of sodium influx, the intrinsic properties of the channels themselves, or both? These experiments will utilize whole-cell and inside-out patch clamp recordings from isolated chick midbrain neurons and ciliary ganglion neurons. Second, what are the pharmacological properties of IK(Na)? These experiments will examine the effects of several known potassium-channel blocking agents, using whole- cell recordings from isolated chick neurons. These results will allow comparison of IK(Na) with other potassium currents described previously. In addition, these experiments may contribute to an understanding of the precise role of IK(Na) in regulating voltage- dependent electrical behavior in excitable cells. Third, the role of IK(Na) in modulating responses to certain neurotransmitters will be examined by means of whole-cell recordings from isolated chick neurons. These experiments will indicate the extent to which IK(Na) contributes to the process of synaptic transmission. Finally, the distribution of IK(Na) will be examined by means of whole-cell recordings from neurons isolated from several regions of the chick central and peripheral nervous systems. These experiments will determine whether IK(Na) is a widespread ionic conductance and also whether its properties are uniform in all cells where it is present. Insofar as IK(Na) is a fundamental mechanism for regulating the electrical behavior of excitable cells, these results could be applicable to a wide variety of disease states. However, the results should be especially applicable to diseases such aa epilepsy, where the normal mechanisms for regulating the electrical behavior of neurons, and especially of repetitive firing, appear to be abnormal.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
First Independent Research Support & Transition (FIRST) Awards (R29)
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Neurology B Subcommittee 2 (NEUB)
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Florida State University
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Levey, M S; Brumwell, C L; Dryer, S E et al. (1995) Innervation and target tissue interactions differentially regulate acetylcholine receptor subunit mRNA levels in developing neurons in situ. Neuron 14:153-62
Raucher, S; Dryer, S E (1995) Target-derived factors regulate the expression of Ca(2+)-activated K+ currents in developing chick sympathetic neurones. J Physiol 486 ( Pt 3):605-14
D'Souza, T; Dryer, S E (1994) Intracellular free Ca2+ in dissociated cells of the chick pineal gland: regulation by membrane depolarization, second messengers and neuromodulators, and evidence for release of intracellular Ca2+ stores. Brain Res 656:85-94
Dryer, S E (1994) Functional development of the parasympathetic neurons of the avian ciliary ganglion: a classic model system for the study of neuronal differentiation and development. Prog Neurobiol 43:281-322
Dryer, S E (1994) Na(+)-activated K+ channels: a new family of large-conductance ion channels. Trends Neurosci 17:155-60
Dourado, M M; Brumwell, C; Wisgirda, M E et al. (1994) Target tissues and innervation regulate the characteristics of K+ currents in chick ciliary ganglion neurons developing in situ. J Neurosci 14:3156-65
Raucher, S; Dryer, S E (1994) Functional expression of A-currents in embryonic chick sympathetic neurones during development in situ and in vitro. J Physiol 479 ( Pt 1):77-93
Wisgirda, M E; Dryer, S E (1994) Functional dependence of Ca(2+)-activated K+ current on L- and N-type Ca2+ channels: differences between chicken sympathetic and parasympathetic neurons suggest different regulatory mechanisms. Proc Natl Acad Sci U S A 91:2858-62
Dourado, M M; Dryer, S E (1994) Regulation of A-currents by cell-cell interactions and neurotrophic factors in developing chick parasympathetic neurones. J Physiol 474:367-77
Dryer, S E; Henderson, D (1993) Cyclic GMP-activated channels of the chick pineal gland: effects of divalent cations, pH, and cyclic AMP. J Comp Physiol A 172:271-9

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