Exemplary Introduction Draft 2
Author: Catherine Osborn
Introduction: Model of Ionic Currents of Hypoglossal Motoneuron
The hypoglossal motoneuron innervates the intrinsic muscles of the tongue and are involved in a variety of behaviors including breathing, chewing, and swallowing. [1] Understanding the respiratory control of the hypoglossal motoneuron is important because of its involvement in maintaining openness of airways during normal breathing and especially during sleep. [2] [3] Age-related changes in these motoneurons, such as age-dependent serotonin receptors, have been associated with the pathogenesis of obstructive sleep apnea. [4] [5] However, other age-dependent changes in neurogenic activity of hypoglossal motoneurons have been reported in rats.
The model we will be recreating, described by Purvis and Butera [6], was constructed to explain the age dependent-changes in action potential firing of the hypoglossal motoneuron. These motoneurons have several different types of currents, some of which that are affected by age. In addition to the sodium and potassium currents, there are several different types of calcium channels as well as a calcium-dependent potassium channel. The persistent inward currents in neonatal rat hypoglossal motoneurons, are mediated predominantly by calcium channels. [7] The calcium currents included in the model we will replicate include the N- and P-type high-voltage-activated calcium currents. There also exists L-type channels that carry only about 5–7% of the total calcium current measured in neonatal rats, which will not be included, although the density of this channel increases with age. [8] [9]. Additionally, the density of the hyperpolarization-activated channel also increases with age. [10]
These age-dependent changes in current density have been associated changes in the action potential firing patterns seen in adult rats. The overall hypothesis of this paper is that changes in the densities of the ionic currents within the rat hypoglossal are responsible for the age-dependent changes seen in the excitability of the neuron, such as a decrease in input resistance [11], the switch from a decrementing firing pattern to an incrementing firing pattern [12], and decreases in the duration of the medium-duration afterhyperpolarization phase of the action potentials. [13]
The Purvis and Butera model of the rat hypoglossal uses the Hodgkin-Huxley formulation of a single-cell compartment [14] and includes the fast sodium and delayed-rectifier potassium currents, high- and low-voltage-activated calcium currents, voltage- and calcium- dependent potassium currents, a hyperpolarization-activated cationic current, and a persistent sodium current.[15] The change in intercellular calcium in this model follows Michalis-Menten mechanics, and the parameters used in this model were determined experimentally. We can use the model to reproduce the neuron’s response apamin, a neurotoxic component of bee venom, which blocks the calcium-dependent potassium channels, [16] and can vary the densities of the included currents to elicit the specific action potential dynamics seen within the adult rat hypoglossal motoneuron.
Notes
- ↑ Eased, K., D. Robinson, S. Selvaratnam, C. Walsh, A. McMorland, and G. Funk. (2001), Modulation of hypoglossal motoneuron excitability by NK1 receptor activation in neonatal mice in vitro. J of Physiol, 534(2):447–464
- ↑ Remmers, J., W. deGroot, E. Sauerland, A. Anch. (1978) Pathogenesis of upper airway occlusion during sleep. J Appl Physiol. 44: 931-8.
- ↑ Fregosi, F. and D. Fuller. (1997) Respiratory-related control of extrinsic tongue muscle activity. Respir Physiol. 110(2-3):295-306.
- ↑ Behan, M. and M. Brownfield. (1999) Age-related changes in serotonin in the hypoglossal nucleus of rat: implications for sleep-disordered breathing. Neuroscience Letters. 267(2):133-136.
- ↑ Zabka, A., M. Behan, and G. Mitchell. (2001) Long term facilitation of respiratory motor output decreases with age in male rats. J of Physiol. 531:509-514.
- ↑ Purvis, L., and R. Butera. (2005) Ionic current model of a hypoglossal motoneuron. J Neurophysiol. 93(2):723-733
- ↑ Viana F., D. Bayliss, and A. Berger. (1993) Calcium conductances and their role in the firing behavior of neonatal rat hypoglossal motoneurons. J Neurophysiol. 69: 2137–2149.
- ↑ Plant, T., C. Schirra, E. Katz, O. Uchitel, and A. Konnerth. (1998) Single-Cell RT-PCR and Functional Characterization of Ca2+ Channels in Motoneurons of the Rat Facial Nucleus. J of Neurosci . 18(23): 9573-9584.
- ↑ Umemiya, M. and A. Berger. (1994) Properties and function of low- and high-voltage-activated calcium channels in hypoglossal motoneurons. J Neurosci 15: 5652–5660
- ↑ Bayliss, D., F. Viana, M. Bellingham, and A. Berger. (1994) Characteristics and postnatal development of a hyperpolarization-activated inward current in rat hypoglossal motoneurons in vitro. J Neurophysiol. 71: 119–128.
- ↑ Viana, F., D. Bayliss, and A. Berger. (1994) Postnatal changes in rat hypoglossal motoneuron membrane properties. Neuroscience. 59: 131–148
- ↑ Viana, F., D. Bayliss, and A. Berger. (1995) Repetitive firing properties of developing rat brainstem motoneurones. J Physiol. 486: 745–761.
- ↑ Lape, R., and A. Nistri. (2000) Current and voltage clamp studies of the spike medium afterhyperpolarization of hypoglossal motoneurons in a rat brain stem slice preparation. J Neurophysiol. 83: 2987–2995 .
- ↑ Hodgkin, A. and A. Huxley. (1952) A quantitative description of membrane current and its application to conduction and excitation in a nerve. J Physiol 117:500–544
- ↑ Purvis, L., and R. Butera. (2005) Ionic current model of a hypoglossal motoneuron. J Neurophysiol. 93(2):723-733
- ↑ Blatz, A. and K. Magleby. (1986) Single apamin-blocked Ca-activated K+ channels of small conductance in cultured rat skeletal muscle. Nature. 323:718-720.
