Membrane Resting Potential of Thalamocortical Relay Neurons Is Shaped by the Interaction Among TASK3 and HCN2 Channels

2006 ◽  
Vol 96 (3) ◽  
pp. 1517-1529 ◽  
Author(s):  
Sven G. Meuth ◽  
Tatyana Kanyshkova ◽  
Patrick Meuth ◽  
Peter Landgraf ◽  
Thomas Munsch ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Standard Procedure ◽  
Resting Potential ◽  
Immunocytochemical Staining ◽  
Equilibrium Potential ◽  
Resting Membrane Potential ◽  
Hcn Channels ◽  
Extracellular Acidification ◽  
Knock Out ◽  
Task Channels

By combining molecular biological, electrophysiological, immunological, and computer modeling techniques, we here demonstrate a counterbalancing contribution of TASK channels, underlying hyperpolarizing K+ leak currents, and HCN channels, underlying depolarizing Ih, to the resting membrane potential of thalamocortical relay (TC) neurons. RT-PCR experiments revealed the expression of TASK1, TASK3, and HCN1–4. Quantitative determination of mRNA expression levels and immunocytochemical staining demonstrated that TASK3 and HCN2 channels represent the dominant thalamic isoforms and are coexpressed in TC neurons. Extracellular acidification, a standard procedure to inhibit TASK channels, blocked a TASK current masked by additional action on HCN channels. Only in the presence of the HCN blocker ZD7288 was the pH-sensitive component typical for a TASK current, i.e., outward rectification and current reversal at the K+ equilibrium potential. In a similar way extracellular acidification was able to shift the activity pattern of TC neurons from burst to tonic firing only during block of Ih or genetic knock out of HCN channels. A single compartmental computer model of TC neurons simulated the counterbalancing influence of TASK and HCN on the resting membrane potential. It is concluded that TASK3 and HCN2 channels stabilize the membrane potential by a mutual functional interaction, that the most efficient way to regulate the membrane potential of TC neurons is the converse modulation of TASK and HCN channels, and that TC neurons are potentially more resistant to insults accompanied by extracellular pH shifts in comparison to other CNS regions.

scholarly journals Current Separations in Myxicola Giant Axons

1969 ◽  
Vol 54 (6) ◽  
pp. 741-754 ◽  
Author(s):  
L. Goldman ◽  
L. Binstock
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Reversal Potential ◽  
Transient Current ◽  
Resting Potential ◽  
Equilibrium Potential ◽  
Resting Membrane Potential ◽  
Concentration Data ◽  
Giant Axons ◽  
Current Reversal

The effect of reducing the external sodium concentration, [Na]o, on resting potential, action potential, membrane current, and transient current reversal potential in Myxicola giant axons was studied. Tris chloride was used as a substitute for NaCl. Preliminary experiments were carried out to insure that the effect of Tris substitution could be attributed entirely to the reduction in [Na]o. Both choline and tetramethylammonium chloride were found to have additional effects on the membrane. The transient current is carried largely by Na, while the delayed current seems to be independent of [Na]o. Transient current reversal potential behaves much like a pure Nernst equilibrium potential for sodium. Small deviations from this behavior are consistent with the possibility of some small nonsodium component in the transient current. An exact PNa/PK for the transient current channels could not be computed from these data, but is certainly well greater than unity and possibly quite large. The peak of the action potential varied with [Na]o as expected for a sodium action potential with some substantial potassium permeability at the time of peak. Resting membrane potential is independent of [Na]o. This finding is inconsistent with the view that the resting membrane potential is determined only by the distribution of K and Na, and PNa/PK. It is suggested that PNa/PK's obtained from resting membrane potential-potassium concentration data do not always have the physical meaning generally attributed to them.

Screening Technologies for Inward Rectifier Potassium Channels: Discovery of New Blockers and Activators

2020 ◽  
Vol 25 (5) ◽  
pp. 420-433 ◽  
Author(s):  
Kenneth B. Walsh
Keyword(s):  
Membrane Potential ◽  
G Protein ◽  
Critical Role ◽  
Inward Rectifier ◽  
Resting Potential ◽  
Equilibrium Potential ◽  
Inward Rectification ◽  
Resting Membrane Potential ◽  
Kir Channels ◽  
Inward Rectifier Potassium Channels

K+ channels play a critical role in maintaining the normal electrical activity of excitable cells by setting the cell resting membrane potential and by determining the shape and duration of the action potential. In nonexcitable cells, K+ channels establish electrochemical gradients necessary for maintaining salt and volume homeostasis of body fluids. Inward rectifier K+ (Kir) channels typically conduct larger inward currents than outward currents, resulting in an inwardly rectifying current versus voltage relationship. This property of inward rectification results from the voltage-dependent block of the channels by intracellular polyvalent cations and makes these channels uniquely designed for maintaining the resting potential near the K+ equilibrium potential (EK). The Kir family of channels consist of seven subfamilies of channels (Kir1.x through Kir7.x) that include the classic inward rectifier (Kir2.x) channel, the G-protein-gated inward rectifier K+ (GIRK) (Kir3.x), and the adenosine triphosphate (ATP)-sensitive (KATP) (Kir 6.x) channels as well as the renal Kir1.1 (ROMK), Kir4.1, and Kir7.1 channels. These channels not only function to regulate electrical/electrolyte transport activity, but also serve as effector molecules for G-protein-coupled receptors (GPCRs) and as molecular sensors for cell metabolism. Of significance, Kir channels represent promising pharmacological targets for treating a number of clinical conditions, including cardiac arrhythmias, anxiety, chronic pain, and hypertension. This review provides a brief background on the structure, function, and pharmacology of Kir channels and then focuses on describing and evaluating current high-throughput screening (HTS) technologies, such as membrane potential-sensitive fluorescent dye assays, ion flux measurements, and automated patch clamp systems used for Kir channel drug discovery.

scholarly journals The Influence of H+ on the Membrane Potential and Ion Fluxes of Nitella

1968 ◽  
Vol 52 (1) ◽  
pp. 60-87 ◽  
Author(s):  
Hiroshi Kitasato
Keyword(s):  
Membrane Potential ◽  
Membrane Conductance ◽  
Potential Difference ◽  
Potential Change ◽  
Resting Potential ◽  
Equilibrium Potential ◽  
Resting Membrane Potential ◽  
Ph Change ◽  
Ph Changes ◽  
External Ph

The resting membrane potential of the Nitella cell is relatively insensitive to [K]o, but behaves like a hydrogen electrode. K+ and Cl- effluxes from the cell were measured continuously, while the membrane potential was changed either by means of a negative feedback circuit or by external pH changes. The experiments indicate that PK and PCl are independent of pH but are a function of membrane potential. Slope ion conductances, GK, GCl, and GNa were calculated from efflux measurements, and their sum was found to be negligible compared to membrane conductance. The possibility that a boundary potential change might be responsible for the membrane potential change was considered but was ruled out by the fact that the peak of the action potential remained at a constant level regardless of pH changes in the external solution. The conductance for H+ was estimated by measuring the membrane current change during an external pH change while the membrane potential was clamped at K+ equilibrium potential. In the range of external pH 5 to 6, H+ chord conductance was substantially equal to the membrane conductance. However, the [H]i measured by various methods was not such as would be predicted from the [H]o and the membrane potential using the Nernst equation. In artificial pond water containing DNP, the resting membrane potential decreased; this suggested that some energy-consuming mechanism maintains the membrane potential at the resting level. It is probable that there is a H+ extrusion mechanism in the Nitella cell, because the potential difference between the resting potential and the H+ equilibrium potential is always maintained notwithstanding a continuous H+ inward current which should result from the potential difference.

Beta-adrenergic actions on membrane electrical properties of dissociated smooth muscle cells

1988 ◽  
Vol 254 (3) ◽  
pp. C423-C431 ◽  
Author(s):  
H. Yamaguchi ◽  
T. W. Honeyman ◽  
F. S. Fay
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Electrical Properties ◽  
Smooth Muscle Cells ◽  
Input Resistance ◽  
Muscle Cells ◽  
Resting Potential ◽  
Equilibrium Potential ◽  
Dependent Manner ◽  
Beta Adrenergic

Studies were carried out to determine the effects of the beta-adrenergic agent, isoproterenol (ISO), on membrane electrical properties in single smooth muscle cells enzymatically dispersed from toad stomach. In cells bathed in buffer of physiological composition, the average resting potential was -56.4 +/- 1.4 mV (mean +/- SE, n = 35). The dominant effect of exposure to ISO was hyperpolarization. The hyperpolarization was apparent in all cells studied and averaged 11.6 +/- 1.2 mV (n = 27). In the majority of the cells, hyperpolarization was accompanied by a decreased input resistance (Rin). Often the change in resistance appeared to lag behind the change in membrane potential. The lack of coincident changes in membrane potential and resistance may reflect a superposition of the outward rectification properties of the membrane on beta-adrenergic-induced increases in ionic conductance. In about half of the cells, an initial small depolarization (3.1 +/- 0.3 mV, n = 14) was accompanied by a small but distinct increase in Rin (12 +/- 2.5%). When membrane potential was made more negative than the estimated equilibrium potential for K+ (EK) by injection of current, ISO also produced biphasic effects, an initial hyperpolarization which reversed to a sustained depolarization to a value (-90 mV) near the estimated EK. The hyperpolarization by ISO could be diminished in a time-dependent manner by previous exposure to ouabain. The inhibition by ouabain, however, appeared to be a fortuitous result of glycoside-induced positive shifts in EK. These observations indicate that the dominant electrophysiological effect of beta-adrenergic stimuli is to hyperpolarize the cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Ca2+-activated Cl− current in cultured myenteric neurons from murine proximal colon

2003 ◽  
Vol 284 (4) ◽  
pp. C839-C847 ◽  
Author(s):  
Sok Han Kang ◽  
Pieter Vanden Berghe ◽  
Terence K. Smith
Keyword(s):  
Membrane Potential ◽  
Channel Blocker ◽  
Reversal Potential ◽  
Outward Current ◽  
Proximal Colon ◽  
Time Dependent ◽  
Equilibrium Potential ◽  
Resting Membrane Potential ◽  
Myenteric Neurons ◽  
Whole Cell Patch Clamp

Whole cell patch-clamp recordings were made from cultured myenteric neurons taken from murine proximal colon. The micropipette contained Cs+ to remove K+ currents. Depolarization elicited a slowly activating time-dependent outward current ( I tdo), whereas repolarization was followed by a slowly deactivating tail current ( I tail). I tdo and I tail were present in ∼70% of neurons. We identified these currents as Cl− currents ( I Cl), because changing the transmembrane Cl− gradient altered the measured reversal potential ( E rev) of both I tdo and I tail with that for I tailshifted close to the calculated Cl− equilibrium potential ( E Cl). I Cl are Ca2+-activated Cl− current [ I Cl(Ca)] because they were Ca2+dependent. E Cl, which was measured from the E rev of I Cl(Ca) using a gramicidin perforated patch, was −33 mV. This value is more positive than the resting membrane potential (−56.3 ± 2.7 mV), suggesting myenteric neurons accumulate intracellular Cl−. ω-Conotoxin GIVA [0.3 μM; N-type Ca2+ channel blocker] and niflumic acid [10 μM; known I Cl(Ca) blocker], decreased the I Cl(Ca). In conclusion, these neurons have I Cl(Ca) that are activated by Ca2+entry through N-type Ca2+ channels. These currents likely regulate postspike frequency adaptation.

scholarly journals Relative Ion Permeabilities in the Crayfish Giant Axon Determined from Rapid External Ion Changes

1967 ◽  
Vol 50 (7) ◽  
pp. 1929-1953 ◽  
Author(s):  
Alfred Strickholm ◽  
B. Gunnar Wallin
Keyword(s):  
Membrane Potential ◽  
Potassium Level ◽  
Potassium Concentration ◽  
Giant Axon ◽  
Resting Potential ◽  
Resting Membrane Potential ◽  
Constant Field ◽  
Appreciable Effect ◽  
Ion Concentrations ◽  
External Potassium

The changes in membrane potential of isolated, single crayfish giant axons following rapid shifts in external ion concentrations have been studied. At normal resting potential the immediate change in membrane potential after a variation in external potassium concentration is quite marked compared to the effect of an equivalent chloride change. If the membrane is depolarized by a maintained potassium elevation, the immediate potential change due to a chloride variation becomes comparable to that of an equivalent potassium change. There is no appreciable effect on membrane potential when external sodium is varied, at normal or at a depolarized membrane potential. Starting from the constant field equation, expressions for the permeability ratios PCl/PK, PNa/PK, and for intracellular potassium and chloride concentrations are derived. At normal resting membrane potential, PCl/PK is 0.13 but at a membrane potential of -53 mv (external potassium level increased about five times) it is 0.85. The intracellular concentrations of potassium and chloride are estimated to be 233 and 34 mM, respectively, and it is pointed out that this is not compatible with ions distributed in a Nernst equilibrium across the membrane. It is also stressed that the information given by a plot of membrane potential vs. the logarithm of external potassium concentrations is very limited and rests upon several important assumptions.

Control of intracellular calcium by membrane potential in human melanoma cells

1993 ◽  
Vol 265 (6) ◽  
pp. C1501-C1510 ◽  
Author(s):  
B. Nilius ◽  
G. Schwarz ◽  
G. Droogmans
Keyword(s):  
Cell Proliferation ◽  
Membrane Potential ◽  
Intracellular Calcium ◽  
Reversal Potential ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Resting Potential ◽  
Equilibrium Potential ◽  
Patch Clamp Technique ◽  
Human Melanoma Cells

The modulation of intracellular calcium ([Ca2+]i) by the membrane potential was investigated in human melanoma cells by combining the nystatin-perforated patch-clamp technique with Ca2+ measurements. Voltage steps to -100 mV induced a rise in [Ca2+]i and a creeping inward current. These effects were absent in Ca(2+)-free solution and could be blocked by Ni2+ or La3+. Voltage ramps revealed a close correlation between [Ca2+]i and voltage, with the strongest voltage dependence around the resting potential. Long-lasting tail currents, closely correlated with the rise in [Ca2+]i and a reversal potential close to the K+ equilibrium potential, occurred if the membrane potential was clamped back to 0 mV. They were absent if intracellular K+ was replaced by Cs+ and blocked by extracellular tetraethylammonium (5 mM), Ba2+ (1 mM), or a membrane-permeable adenosine 3',5'-cyclic monophosphate analogue. These observations are discussed in relation to cell proliferation. The enhanced expression of K+ channels during cell proliferation provides a positive-feedback mechanism resulting in long-term changes in [Ca2+]i required for the G1-S transition in the cell cycle.

Electrical properties of frog motoneurons in the in situ spinal cord

1976 ◽  
Vol 39 (3) ◽  
pp. 459-473 ◽  
Author(s):  
P. C. Magherini ◽  
W. Precht
Keyword(s):  
Spinal Cord ◽  
Membrane Potential ◽  
Electrical Properties ◽  
Rana Temporaria ◽  
Reversal Potential ◽  
Input Resistance ◽  
Resting Potential ◽  
Equilibrium Potential ◽  
Spike Initiation

Electrical properties of the spinal motoneurons of Rana temporaria and R. esculenta were investigated in the in situ spinal cord at 20-22 degrees C by means of intracellular recording and current injection. Input resistance values depended on the method of measurement in a given cell but were generally inversely related to axon conduction velocity. The membrane-potential response to a subthreshold current pulse was composed of at least two exponentials with mean time constants of 2.5 and 20 ms. The membrance potential reached by the peak of a spike depended on the mode of spike initiation and membrane potential. Preceding a suprathreshold depolarization by a hyperpolarizing pulse could delay and eliminate spike initiation, similar to effects reported in certain invertebrate neurons. Antidromic invasion frequently failed in motoneurons of normal resting potential. Antidromic spike components (m,IS, SD) were similar to those of cat motoneurons. The delayed depolarization and the long afterhyperpolarization following an antidromic spike had many properties in common with the analogous afterpotentials of cat motoneurons. The reversal potential of the short afterhyperpolarization occurring immediately after the spike varied with resting potential and could not be used to determine potassium equilibrium potential. Sustained rhythmic firing could be evoked by continuous synaptic drive or long pulses of injected current. The plot of firing rate versus current strength had a substantial linear region. Both steady firing and adaptation properties varied markedly with motoneuron input resistance.

Effect of procaine on electrical properties of squid axon membrane

1959 ◽  
Vol 196 (5) ◽  
pp. 1071-1078 ◽  
Author(s):  
Robert E. Taylor
Keyword(s):  
Steady State ◽  
Membrane Potential ◽  
Electrical Properties ◽  
Potassium Conductance ◽  
Resting Potential ◽  
Equilibrium Potential ◽  
Squid Axon ◽  
Voltage Step ◽  
Axon Membrane ◽  
Rate Of Development

Procaine (0.025–0.1%; pH 7.9) caused a reduction in the amount and rate of development of the early transient (sodium) and late steady state (potassium) currents which occur during a depolarizing voltage step applied to the excised, voltage clamped squid axon. Consistent results were obtained by holding the membrane potential at a hyperpolarized value prior to the applied step. No effect was seen on the resting potential, on the sodium equilibrium potential, or on the proportion of the sodium carrying system which was ‘inactive’ at any membrane potential. The blocking action of procaine is a result of the inhibition by the drug of the sodium carrying system. The effect of procaine on the potassium conductance is such as to oppose the blocking action.

scholarly journals Effects of Some Inhibitors on the Temperature-Dependent Component of Resting Potential in Lobster Axon

1967 ◽  
Vol 50 (7) ◽  
pp. 1835-1848 ◽  
Author(s):  
Joseph P. Senft
Keyword(s):  
Membrane Potential ◽  
Electrode Potential ◽  
Potassium Ion ◽  
Potential Change ◽  
Resting Potential ◽  
Resting Membrane Potential ◽  
Ion Pump ◽  
Perfusion Medium ◽  
Axon Membrane ◽  
Electrogenic Ion Pump

The resting membrane potential of the lobster axon becomes 5–8 mv more negative when the temperature of the perfusion solution is increased 10°C. This potential change is about twice that predicted if the axon membrane potential followed that expected for a potassium ion electrode potential. When the inhibitors, 2, 4-dinitrophenol, sodium cyanide, and sodium azide, were added separately to the perfusion medium the potential change was reduced to about 1.4 times that predicted for a potassium ion electrode potential. Assays of axons exposed to these inhibitors showed that ATP levels were reduced to about one-fourth that obtained for control axons. Ouabain added to the perfusion medium reduced the potential change to that expected for a potassium ion electrode potential. These results suggest that the resting potential changes with temperature as a result of the activity of an electrogenic ion pump.

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