Biomaterial Database

A model of the T-type calcium current and the low-threshold spike in thalamic neurons. 1991

X J Wang, and J Rinzel, and M A Rogawski

Mathematical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.

1. A model of the transient, low-threshold voltage-dependent (T-type) Ca2+ current is constructed using recent whole-cell voltage-clamp data from enzymatically isolated rat thalamocortical relay neurons. The T-type Ca2+ current is described according to the Hodgkin-Huxley scheme, using the m3h format, with rate constants determined from the experimental data (22-24 degrees C; extracellular Ca2+ concentration [Ca2+]o = 3 mM). 2. The T-type Ca2+ current inactivates rapidly during maintained depolarization (time constant, Tau h approximately 20 ms at -20 mV), yet recovery from inactivation is slow (time constant, Tau r approximately 270 ms at -80 mV). To reconcile these observations, a two-step kinetic scheme is proposed for the inactivation gate. Each of the time constants in this scheme is voltage dependent, with a maximum at about -85 mV (45 ms for one and 275 ms for the other). 3. Numerical simulations of recovery in a two-pulse, voltage-clamp protocol compare favorably with experimental results obtained by Coulter et al. as well as those obtained in an independent series of experiments with guinea pig thalamic neurons ([Ca2+]o = 10 mM). 4. For current-clamp simulations, a leakage current gL (V-VL) is included; with VL = -65 mV, the calculated resting membrane potential is -63 mV. 5. It is shown that the T-type Ca2+ current together with the leakage current suffices to describe the low-threshold spike (LTS), a slow, triangular-shaped depolarizing event that can be evoked only from relatively hyperpolarized membrane potentials and that underlies the burst firing of Na(+)-dependent action potentials in thalamic neurons. Outward currents are not required to reproduce the basic shape of the LTS. 6. The LTS can be activated with either a depolarizing current step from a sufficiently hyperpolarized level or on termination of a hyperpolarizing current step. In either case, the amplitude of the LTS is a monotonically increasing, sigmoid-shape function of the hyperpolarizing current step intensity. 7. Because of the slower kinetic step of the channel's inactivation gate, our model predicts that recovery of the LTS to greater than one-half amplitude would require a prolonged hyperpolarization of greater than 100 ms (at body temperature). This imposes an upper limit (approximately 10 Hz) on the frequency of repetitive hyperpolarization that can elicit a train of LTSs and hence on the frequency of any rhythm that requires LTS-mediated bursting of thalamic neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008564	Membrane Potentials	The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).	Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D008959	Models, Neurological	Theoretical representations that simulate the behavior or activity of the neurological system, processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.	Neurologic Models,Model, Neurological,Neurologic Model,Neurological Model,Neurological Models,Model, Neurologic,Models, Neurologic
D008962	Models, Theoretical	Theoretical representations that simulate the behavior or activity of systems, processes, or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.	Experimental Model,Experimental Models,Mathematical Model,Model, Experimental,Models (Theoretical),Models, Experimental,Models, Theoretic,Theoretical Study,Mathematical Models,Model (Theoretical),Model, Mathematical,Model, Theoretical,Models, Mathematical,Studies, Theoretical,Study, Theoretical,Theoretical Model,Theoretical Models,Theoretical Studies
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D012032	Refractory Period, Electrophysiological	The period of time following the triggering of an ACTION POTENTIAL when the CELL MEMBRANE has changed to an unexcitable state and is gradually restored to the resting (excitable) state. During the absolute refractory period no other stimulus can trigger a response. This is followed by the relative refractory period during which the cell gradually becomes more excitable and the stronger impulse that is required to illicit a response gradually lessens to that required during the resting state.	Period, Neurologic Refractory,Periods, Neurologic Refractory,Refractory Period, Neurologic,Tetanic Fade,Vvedenskii Inhibition,Wedensky Inhibition,Inhibition, Vvedenskii,Inhibition, Wedensky,Neurologic Refractory Period,Neurologic Refractory Periods,Neuromuscular Fade,Neuromuscular Transmission Fade,Refractory Period, Neurological,Refractory Periods, Neurologic,Electrophysiological Refractory Period,Electrophysiological Refractory Periods,Fade, Neuromuscular,Fade, Neuromuscular Transmission,Fade, Tetanic,Neurological Refractory Period,Neurological Refractory Periods,Refractory Periods, Electrophysiological,Refractory Periods, Neurological,Transmission Fade, Neuromuscular
D012044	Regression Analysis	Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see LINEAR MODELS) the relationship is constrained to be a straight line and LEAST-SQUARES ANALYSIS is used to determine the best fit. In logistic regression (see LOGISTIC MODELS) the dependent variable is qualitative rather than continuously variable and LIKELIHOOD FUNCTIONS are used to find the best relationship. In multiple regression, the dependent variable is considered to depend on more than a single independent variable.	Regression Diagnostics,Statistical Regression,Analysis, Regression,Analyses, Regression,Diagnostics, Regression,Regression Analyses,Regression, Statistical,Regressions, Statistical,Statistical Regressions
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000200	Action Potentials	Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.	Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia