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Applying the Pump and Leak Hypothesis. An experimental and theoretical investigation of the principles of ion regulation and excitability in the crustacean stretch receptor neuron.

Theander, Sten LU (1998)
Abstract
An invertebrate nerve cell preparation, the lobster stretch receptor neuron, was investigated with respect to maintenance of its resting voltage, intracellular ion concentrations and excitability using voltage clamp technique and ion-selective microelectrodes. It was found that the resting voltage (-65 mV) of microelectrode impaled cells is caused by (a) a homogenous population of K+ channels which we denoted as leak channels (b) an electrogenic and voltage-dependent Na-K pump current and (c) an inward microelectrode-induced "impalement" current carried mainly by Na+. Together, these currents comprise a non-dynamic "instantaneous current. Among the results pertaining to the leak current, its sensitivity (enhancement) to increases of [K+]o... (More)
An invertebrate nerve cell preparation, the lobster stretch receptor neuron, was investigated with respect to maintenance of its resting voltage, intracellular ion concentrations and excitability using voltage clamp technique and ion-selective microelectrodes. It was found that the resting voltage (-65 mV) of microelectrode impaled cells is caused by (a) a homogenous population of K+ channels which we denoted as leak channels (b) an electrogenic and voltage-dependent Na-K pump current and (c) an inward microelectrode-induced "impalement" current carried mainly by Na+. Together, these currents comprise a non-dynamic "instantaneous current. Among the results pertaining to the leak current, its sensitivity (enhancement) to increases of [K+]o deserves mention since it may provide an important voltage stabilization in conditions of increased [K+]o. From extracellular recordings on unimpaled cells, it could also be concluded that native cells are more polarized, by ~10 mV, than impaled cells. At this voltage an inwardly rectifying current so-called Q-current is also active and function as dynamic stabilizer of the resting voltage. In connection with investigations pertaining to the leak current a previously not described outward current, resembling so-called A-currents was found. In comparing the kinetics of this current (the A-current) in slowly and rapidly adapting cells, marked differences were found. Both activation and inactivation of the A-current was found to be set at more negative voltages in the rapidly adapting cell causing the A-current to be stronger in this kind of cell. The cell's Cl- homeostasis which, among other things, is a prerequisite for normal function of the cell's inhibitory system, was investigated. It was found that the main determinant of [Cl-]i is a DIDS-sensitive K-Cl cotransporter. Evidence for a Cl-HCO3 exchanger as well as for an electrogenic Na-HCO3 cotransporter was also found.



An important part in each of the investigations was the formulation of mathematical models for those membrane currents and ion transporters which were investigated quantitatively. These models were integrated into a model of the cells excitability and ion turnover, which well reproduces experimental findings. (Less)
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author
supervisor
opponent
  • Professor Sandblom, John
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Neurology, neuropsychology, lobster, stretch receptor neuron, leak current, Q-current, K-Cl cotransporter, A-current, mathematical model, excitability, GABA channel, neurophysiology, ion regulation, neuropsykologi, Neurologi, neurofysiologi
pages
145 pages
publisher
Lund University
defense location
N/A
defense date
1998-01-16 10:15:00
external identifiers
  • other:ISRN: LUMEDW/MFF--1015--SE
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Division of Physiotherapy (Closed 2012) (013042000)
id
24bfdd6b-3a5c-4d9e-8c79-4243509af179 (old id 38476)
date added to LUP
2016-04-04 11:02:43
date last changed
2018-11-21 21:02:18
@phdthesis{24bfdd6b-3a5c-4d9e-8c79-4243509af179,
  abstract     = {{An invertebrate nerve cell preparation, the lobster stretch receptor neuron, was investigated with respect to maintenance of its resting voltage, intracellular ion concentrations and excitability using voltage clamp technique and ion-selective microelectrodes. It was found that the resting voltage (-65 mV) of microelectrode impaled cells is caused by (a) a homogenous population of K+ channels which we denoted as leak channels (b) an electrogenic and voltage-dependent Na-K pump current and (c) an inward microelectrode-induced "impalement" current carried mainly by Na+. Together, these currents comprise a non-dynamic "instantaneous current. Among the results pertaining to the leak current, its sensitivity (enhancement) to increases of [K+]o deserves mention since it may provide an important voltage stabilization in conditions of increased [K+]o. From extracellular recordings on unimpaled cells, it could also be concluded that native cells are more polarized, by ~10 mV, than impaled cells. At this voltage an inwardly rectifying current so-called Q-current is also active and function as dynamic stabilizer of the resting voltage. In connection with investigations pertaining to the leak current a previously not described outward current, resembling so-called A-currents was found. In comparing the kinetics of this current (the A-current) in slowly and rapidly adapting cells, marked differences were found. Both activation and inactivation of the A-current was found to be set at more negative voltages in the rapidly adapting cell causing the A-current to be stronger in this kind of cell. The cell's Cl- homeostasis which, among other things, is a prerequisite for normal function of the cell's inhibitory system, was investigated. It was found that the main determinant of [Cl-]i is a DIDS-sensitive K-Cl cotransporter. Evidence for a Cl-HCO3 exchanger as well as for an electrogenic Na-HCO3 cotransporter was also found.<br/><br>
<br/><br>
An important part in each of the investigations was the formulation of mathematical models for those membrane currents and ion transporters which were investigated quantitatively. These models were integrated into a model of the cells excitability and ion turnover, which well reproduces experimental findings.}},
  author       = {{Theander, Sten}},
  keywords     = {{Neurology; neuropsychology; lobster; stretch receptor neuron; leak current; Q-current; K-Cl cotransporter; A-current; mathematical model; excitability; GABA channel; neurophysiology; ion regulation; neuropsykologi; Neurologi; neurofysiologi}},
  language     = {{eng}},
  publisher    = {{Lund University}},
  school       = {{Lund University}},
  title        = {{Applying the Pump and Leak Hypothesis. An experimental and theoretical investigation of the principles of ion regulation and excitability in the crustacean stretch receptor neuron.}},
  year         = {{1998}},
}