Long-lasting reduction of excitability by a sodium-dependent potassium current in cat neocortical neurons

1989 ◽  
Vol 61 (2) ◽  
pp. 233-244 ◽  
Author(s):  
P. C. Schwindt ◽  
W. J. Spain ◽  
W. E. Crill
Keyword(s):  
Voltage Clamp ◽  
Time Course ◽  
Outward Current ◽  
Repetitive Firing ◽  
K Channel ◽  
Channel Blockers ◽  
Dantrolene Sodium ◽  
Current Time ◽  
Tail Current ◽  
Neocortical Neurons

1. The function and ionic mechanism of a slow outward current were studied in large layer V neurons of cat sensorimotor cortex using an in vitro slice preparation and single microelectrode voltage clamp. 2. With Ca2+ influx blocked, a slow relaxation ("tail") of outward current followed either (1) repetitive firing evoked for 1 s or (2) a small 1-s depolarizing voltage clamp step that activated the persistent Na+ current of neocortical neurons, INaP. When a depolarization that activated INaP was maintained, an outward current gradually developed and increased in amplitude over a period of tens of seconds to several minutes. An outward tail current of similar duration followed repolarization. The slow outward current was abolished by TTX, indicating it depended on Na+ influx. 3. With Ca2+ influx blocked, the onset of the slow Na+-dependent outward current caused spike frequency adaptation during current-evoked repetitive firing. Following the firing, the decay of the Na+-dependent current caused a slow afterhyperpolarization (sAHP) and a long-lasting reduction of excitability. It also was responsible for habituation of the response to repeated identical current pulses. 4. The Na+-dependent tail current had properties expected of a K+ current. Membrane chord conductance increased during the tail, and tail amplitude was reduced or reversed by membrane potential hyperpolarization and raised extracellular K+ concentration [( K+]0). 5. The current tail was reduced reversibly by the K+ channel blockers TEA (5-10 mM), muscarine (5-20 microM), and norepinephrine (100 microM). These agents also resulted in a larger, more sustained inward current during the preceding step depolarization. Comparison of current time course before and after the application of blocking agents suggested that, in spite of its capability for slow buildup and decay, the onset of the Na+-dependent outward current occurs within 100 ms of an adequate step depolarization. 6. With Ca2+ influx blocked, extracellular application of dantrolene sodium (30 microM) had no clear effect on the current tail or the corresponding sAHP.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Slow components of potassium tail currents in rat skeletal muscle.

1983 ◽  
Vol 81 (4) ◽  
pp. 513-530 ◽  
Author(s):  
K G Beam ◽  
P L Donaldson
Keyword(s):  
Time Constant ◽  
Time Course ◽  
Outward Current ◽  
Giant Axon ◽  
K Channel ◽  
Tail Current ◽  
Anomalous Rectifier ◽  
Single Well ◽  
Current Flows ◽  
Slow Kinetic

The kinetics of potassium tail currents have been studied in the omohyoid muscle of the rat using the three-microelectrode voltage-clamp technique. The currents were elicited by a two-pulse protocol in which a conditioning pulse to open channels was followed by a test step to varying levels. The tail currents reversed at a single well-defined potential (VK). At hyperpolarized test potentials (-100 mV and below), tail currents were inward and exhibited two clearly distinguishable phases of decay, a fast tail with a time constant of 2-3 ms and a slow tail with a time constant of approximately 150 ms. At depolarized potentials (-60 mV and above), tail currents were outward and did not show two such easily separable phases of decay, although a slow kinetic component was present. The slow kinetic phase of outward tail currents appeared to be functionally distinct from the slow inward tail since the channels responsible for the latter did not allow significant outward current. Substitution of Rb for extracellular K abolished current through the anomalous (inward-going) rectifier and at the same time eliminated the slow inward tail, which suggests that the slow inward tail current flows through anomalous rectifier channels. The amplitude of the slow inward tail was increased and VK was shifted in the depolarizing direction by longer conditioning pulses. The shift in VK implies that during outward currents potassium accumulates in a restricted extracellular space, and it is suggested that this excess K causes the slow inward tail by increasing the inward current through the anomalous rectifier. By this hypothesis, the tail current slowly decays as K diffuses from the restricted space. Consistent with such a hypothesis, the decay of the slow inward tail was not strongly affected by changing temperature. It is concluded that a single delayed K channel is present in the omohyoid. Substitution of Rb for K has little effect on the magnitude or time course of outward current tails, but reduces the magnitude and slows the decay of the fast component of inward tails. Both effects are consistent with a mechanism proposed for squid giant axon (Swenson and Armstrong, 1981): that (a) the delayed potassium channel cannot close while Rb is inside it, and (b) that Rb remains in the channel longer than K.

Whole cell current analyses of pancreatic acinar AR42J cells. I. Voltage- and Ca(2+)-activated currents

1991 ◽  
Vol 260 (5) ◽  
pp. C934-C948 ◽  
Author(s):  
K. Kusano ◽  
H. Gainer
Keyword(s):  
Reversal Potential ◽  
Outward Current ◽  
Pancreatic Acinar Cells ◽  
Equilibrium Potential ◽  
Channel Blockers ◽  
Whole Cell ◽  
Inward Current ◽  
Tail Current ◽  
Ar42j Cells ◽  
Conductance Increase

Voltage- and Ca(2+)-activated whole cell currents were studied in AR42J cells, a clonal cell line derived from rat pancreatic acinar cells, using a patch electrode voltage-clamp technique. Four kinds of ionic currents were identified by their ionic dependencies, pharmacological properties, and kinetic parameters: 1) an outward current flow due mainly to a voltage-dependent K(+)-conductance increase, 2) an initial transient inward current due to an Na(+)-conductance increase, 3) transient and long-duration inward current due to a Ca(2+)-conductance increase, and 4) a slowly activating inward current that persists over the duration of the depolarizing pulse and deactivates slowly upon repolarization, producing a slow inward tail current. The slow inward tail current was particularly robust and was interpreted as due to a Ca(2+)-activated Cl(-)-conductance increase, since 1) the generation of this current was blocked by removing the extracellular Ca2+, applying Ca(2+)-channel blockers (Cd2+, nifedipine), or by lowering the intracellular Ca2+ concentration [( Ca2+]i) with EGTA; and 2) the reversal potential (Erev) of the slow inward tail current was close to 0 mV in the control condition (152 mM [Cl-]o/154 mM [Cl-]i), and changes of the [Cl-]o/[Cl )i ratio shifted the Erev toward the predicted Cl- equilibrium potential.

Calcium-dependent current generating the afterhyperpolarization of hippocampal neurons

1986 ◽  
Vol 55 (6) ◽  
pp. 1268-1282 ◽  
Author(s):  
B. Lancaster ◽  
P. R. Adams
Keyword(s):  
Voltage Clamp ◽  
Hippocampal Neurons ◽  
Hippocampal Slices ◽  
Outward Current ◽  
Pyramidal Cells ◽  
Resting Potential ◽  
Tail Current ◽  
Calcium Dependent ◽  
K Current

A single-electrode voltage-clamp technique was employed on in vitro hippocampal slices to examine the membrane current responsible for the slow afterhyperpolarization (AHP) in CA1 pyramidal cells. This was achieved by using conventional procedures to evoke an AHP in current clamp, followed rapidly by a switch into voltage clamp (hybrid clamp). The AHP current showed a dependence on extracellular K+, which was close to that predicted for a K+ current by the Nernst equation. The AHP current could be blocked by Cd2+ or norepinephrine. Although the AHP current showed a requirement for voltage-dependent Ca2+ entry, the current did not show any clear intrinsic voltage dependence. Once activated, AHP current is not turned off by hyperpolarizing the membrane potential. The effects of norepinephrine, Cd2+, and tetraethylammonium (TEA) were used to identify an AHP current component to the outward current evoked by depolarizing voltage commands from holding potentials that approximate to the resting potential for these cells. The AHP current can contribute significantly to the outward current during the depolarizing command. Upon repolarization it is evident as a slow outward tail current. This slow tail current had the same time constant as AHP currents evoked by hybrid clamp. Fast components to the tail currents were also observed. These were sensitive to Cd2+ and TEA. They probably represent a voltage-sensitive gKCa, sometimes termed C-current. The strong sensitivity to voltage and TEA displayed by the conventionally described gKCa (IC) are properties inconsistent with the AHP. It seems likely that the AHP current (IAHP) represents a Ca2+-activated K+ current separate from IC and that these two currents coexist in the same cell.

scholarly journals Properties of "creep currents" in single frog atrial cells.

1986 ◽  
Vol 87 (6) ◽  
pp. 833-855 ◽  
Author(s):  
J R Hume ◽  
A Uehara
Keyword(s):  
Time Course ◽  
Outward Current ◽  
Membrane Current ◽  
K Channel ◽  
Transient Outward Current ◽  
Ca Channel ◽  
Purkinje Fibers ◽  
Atrial Cells ◽  
Cardiac Purkinje Fibers ◽  
Inward Currents

Changes in membrane current in response to an elevation of [Na]i were studied in enzymatically dispersed frog atrial cells. Na loading by either intracellular dialysis or exposure to the Na ionophore monensin produces changes in membrane current that resemble the "creep currents" originally observed in cardiac Purkinje fibers during exposure to low-K solutions. Na loading induces a transient outward current during depolarizing voltage-clamp pulses, followed by an inward current in response to repolarization back to the holding potential. In contrast to cardiac Purkinje fibers, Na loading of frog atrial cells induces creep currents without accompanying transient inward currents. Creep currents induced by Na loading are insensitive to K channel antagonists like Cs and 4-aminopyridine; they are not influenced by doses of Ca channel antagonists that abolish iCa, but are sensitive to changes in [Ca]o or [Na]o. A comparison of the time course of development of inward creep currents are not tail currents associated with iCa. Inward creep currents can also be induced by experimental interventions that increase the iCa amplitude. Exposure to isoproterenol enhances the iCa amplitude and induces inward creep currents; both can be attenuated by Ca channel antagonists. Both inward and outward creep currents are blocked by low doses of La, independently of La's ability to block iCa. It is concluded that (a) creep currents are not mediated by voltage-gated Na, Ca, or K channels or by an electrogenic Na,K pump; (b) inward creep currents induced either by Na loading or in response to an increase in the amplitude of iCa are triggered by an elevation of [Ca]i; and (c) creep currents may be generated by either an electrogenic Na/Ca exchange mechanism or by a nonselective cation channel activated by [Ca]i.

Diverse current and voltage responses to baclofen in an identified molluscan photoreceptor

1995 ◽  
Vol 74 (2) ◽  
pp. 506-518 ◽  
Author(s):  
L. D. Matzel ◽  
I. A. Muzzio ◽  
R. F. Rogers
Keyword(s):  
Voltage Clamp ◽  
Action Potentials ◽  
Gabab Receptor ◽  
Outward Current ◽  
Gabab Receptors ◽  
Equilibrium Potential ◽  
K Channel ◽  
Electrode Voltage ◽  
Voltage Dependent ◽  
K Current

1. gamma-Aminobuturic acid-B (GABAB) receptors play a role in the mediation of slow inhibitory postsynaptic potentials in mammalian as well as some nonmammalian species. In identified photoreceptors from the marine mollusc Hermissenda, recent evidence has suggested that GABA, as well as the GABAB receptor agonist baclofen, might simultaneously modulate multiple conductances on the postsynaptic membrane. Here, using intracellular current-clamp and single-electrode voltage-clamp techniques, we have characterized responses to baclofen in the B photoreceptors of the Hermissenda eye. 2. Microapplication of baclofen (12.5–62.5 microM) to the terminal branches of the B photoreceptors induced a slow, concentration-dependent hyperpolarization (approximately 3–8 mV) that was accompanied by a cessation of spontaneous action potentials and a positive shift in firing threshold. Both the hyperpolarization and the shift in spike threshold in response to baclofen were attenuated largely by the K+ channel blocker tetraethylammonium chloride (TEA; 50 mM). 3. Bath application of baclofen (100 microM) decreased the amplitude, duration, and the afterhyperpolarization (AHP) of evoked action potentials. Although baclofen's effect on spike duration and amplitude persisted in the absence of extracellular Ca2+, the reduction of the AHP by baclofen was eliminated, suggesting that multiple conductances mediated the baclofen-induced modification of the action potential. 4. Using a single-electrode voltage-clamp technique, microapplication of baclofen to the terminal branches of the B photoreceptor produced a slow, net outward current (< 0.5 nA) that reversed near the equilibrium potential for K+ and shifted to more positive potentials when extracellular K+ was increased, in approximate agreement with the Nernst equation for K+. 5. Baclofen induced an increase in amplitude of the nonvoltage dependent leak conductance (IL), and the increase was blocked by TEA. The baclofen-induced increase of IL was accompanied by an increase in amplitude and a negative shift in the voltage dependence of a slow, steeply voltage-dependent K+ current (IK), which displays selective sensitivity to TEA but does not normally contribute to leak conductance. The amplitude and steady-state inactivation of a fast, transient K+ current, as well as the amplitude of an inwardly rectifying K+ current were unaffected by baclofen. 6. Both the rate of activation as well as the amplitude of a voltage-dependent Ca2+ current (ICa) were reduced by baclofen. The reduction of ICa resulted in a concomitant suppression of a Ca(2+)-dependent K+ current (IK-Ca) that was sufficient to account for the reduction of the AHP after evoked action potentials.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Depletion and accumulation of potassium in the extracellular clefts of cardiac Purkinje fibers during voltage clamp hyperpolarization and depolarization: experiments in sodium-free bathing media.

1977 ◽  
Vol 70 (2) ◽  
pp. 149-169 ◽  
Author(s):  
C M Baumgarten ◽  
G Isenberg ◽  
T F McDonald ◽  
R E Ten Eick
Keyword(s):  
Membrane Potential ◽  
Voltage Clamp ◽  
Driving Force ◽  
Time Course ◽  
Potassium Concentration ◽  
Outward Current ◽  
Voltage Step ◽  
Purkinje Fibers ◽  
Cardiac Purkinje Fibers ◽  
Voltage Dependent

Voltage clamp hyperpolarization and depolarization result in currents consistent with depletion and accumulation of potassium in the extracellular clefts o cardiac Purkinje fibers exposed to sodium-free solutions. Upon hyperpolarization, an inward current that decreased with time (id) was observed. The time course of tail currents could not be explained by a conductance exhibiting voltage-dependent kinetics. The effect of exposure to cesium, changes in bathing media potassium concentration and osmolarity, and the behavior of membrane potential after hyperpolarizing pulses are all consistent with depletion of potassium upon hyperpolarization. A declining outward current was observed upon depolarization. Increasing the bathing media potassium concentration reduced the magnitude of this current. After voltage clamp depolarizations, membrane potential transiently became more positive. These findings suggest that accumulation of potassium occurs upon depolarization. The results indicate that changes in ionic driving force may be easily and rapidly induced. Consequently, conclusions based on the assumption that driving force remains constant during the course of a voltage step may be in error.

Sustained outward current observed after I(to1) inactivation in rabbit atrial myocytes is a novel Cl- current

1992 ◽  
Vol 263 (6) ◽  
pp. H1967-H1971 ◽  
Author(s):  
D. Y. Duan ◽  
B. Fermini ◽  
S. Nattel
Keyword(s):  
Reversal Potential ◽  
Outward Current ◽  
Cell Voltage ◽  
Cell Swelling ◽  
Disulfonic Acid ◽  
K Channel ◽  
Transient Outward Current ◽  
Channel Blockers ◽  
Atrial Myocytes ◽  
K Concentration

In rabbit atrial myocytes, depolarization of the membrane results in a rapidly activating transient outward current (I(to)) that then decays to a sustained level. The sustained current (Isus) remains constant for at least 5 s during continued depolarization. The present study was designed to identify the ionic mechanism underlying Isus with the use of whole cell voltage-clamp techniques. After exposure to 2 mM 4-aminopyridine (4-AP), the 4-AP-sensitive transient outward current (I(to1)) was abolished, but Isus was unaffected. Isus was not blocked by the K+ channel blockers tetraethylammonium chloride and Ba2+, was not changed by increasing superfusate K+ concentration, and was still present when K+ was replaced by Cs+ in both the superfusate and the pipette. Isus was significantly reduced by the Cl- transport blockers 4-acetamido-4'-isothiocyanatostilbene-2.2'-disulfonic acid and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid. The current-voltage relations of Isus showed outward rectification, and the reversal potential of Isus shifted with changes in the transmembrane Cl- gradient in the fashion expected for a Cl- current. We conclude that Isus in rabbit atrium is due to a noninactivating Cl- current which, unlike previously described cardiac Cl- currents, is manifest in the absence of exogenous stimulators of adenosine 3',5'-cyclic monophosphate formation, cytosolic Ca2+ transients, or cell swelling.

Ionic mechanism of substance P actions on neurons in trigeminal root ganglia

1990 ◽  
Vol 64 (1) ◽  
pp. 273-281 ◽  
Author(s):  
I. Spigelman ◽  
E. Puil
Keyword(s):  
Substance P ◽  
Voltage Clamp ◽  
Reversal Potential ◽  
Input Resistance ◽  
K Channel ◽  
Resting Membrane Potential ◽  
Channel Blockers ◽  
Ionic Mechanism ◽  
Trigeminal Root

1. Responses of primary sensory neurons to substance P applications by perfusion were studied with intracellular recording techniques in in vitro slice preparations of trigeminal root ganglia (guinea pigs). Application of substance P in micromolar doses produced reversible depolarizations of 2–47 mV in 48 out of 64 neurons. The depolarizing influence facilitated repetitive spike discharge evoked by current-pulse injection. Evidence of desensitization was observed during prolonged or repeated applications of the peptide. 2. The responses to substance P were associated with decreased input resistance, although increased input resistance was observed in neurons where the resting membrane potential was compensated with DC injection. In single-electrode voltage-clamp (SEVC) recordings, substance P evoked an inward shift in the holding current and reduced an outwardly rectifying component in the I-V relationships. The reversal potential for the substance P response could not be determined. These results suggested that the perikaryal response to substance P has a complex ionic mechanism involving activation and deactivation of membrane conductances. 3. Substance P-induced depolarizations were greatly attenuated during perfusion with solutions that were deficient in [Na+] or [Mg2+] and were not significantly affected during perfusion with low-[Ca2+]-, CO2(+)-containing solutions. 4. In the voltage-clamp investigations, an inward current contributed to the substance P responses during combined application with the K(+)-channel blockers, 4-aminopyridine (4-AP) and tetraethylammonium (TEA). This current was not abolished by the inclusion of CsCl in the perfusing solution or by internal Cs+ application from the recording electrode, suggesting that an anomalous inward rectifier was not involved in the responses to substance P.(ABSTRACT TRUNCATED AT 250 WORDS)

Slowly inactivating outward currents in a cuticular mechanoreceptor neuron of the cockroach (Periplaneta americana)

1995 ◽  
Vol 74 (3) ◽  
pp. 1200-1211 ◽  
Author(s):  
P. H. Torkkeli ◽  
A. S. French
Keyword(s):  
Voltage Clamp ◽  
Time Constant ◽  
Action Potentials ◽  
Periplaneta Americana ◽  
Outward Current ◽  
Equilibrium Potential ◽  
Channel Blockers ◽  
Outward Currents ◽  
Frequency Of Action Potentials ◽  
K Outward Current

1. Although rapid adaptation is a widespread feature of sensory receptors, its ionic basis has not been clearly established in any touch receptor, because their small sizes have severely restricted the range of experiments tat can be performed. In the cockroach tactile spine, intracellular voltage-clamp recordings are now possible. 2. The basic electrophysiological properties of the cockroach femoral tactile spine neuron were studied using discontinuous (switching) single-electrode current- and voltage-clamp recordings. A slowly inactivating voltage-sensitive K+ outward current was detected after the major inward currents were blocked with tetrodotoxin. 3. The total outward current activated in < 1 ms at voltages above 0 mV. At moderate depolarizations it did not inactivate, but at higher depolarizations an inactivation time constant of approximately 260 ms was measured. Some recordings also revealed an additional, slower inactivation time constant of approximately 2.5 s. 4. More than half of the voltage-sensitive K+ outward current could be blocked with the Ca2+ channel blockers Co2+ and Cd2+. Tetraethylammonium chloride (TEA) also reduced the amplitude of the outward current to about half of its original amplitude. The actions of both blockers were reversible and probably reflect overlapping blockades of two separate outward currents. 5. The reversal potentials of the currents that remained after block with Co2+ (-91.7 mV) or TEA (-86.8 mV) were both near the K+ equilibrium potential expected for the tactile spine neuron. The voltage dependencies of activation of the Co(2+)- and TEA-resistant currents were both well fitted by Boltzmann distributions, giving values of half maximal activation (V50) equal to -34.5 mV for the Co(2+)-resistant current and -51.3 mV for the TEA-resistant current. 6. Current-clamp recordings revealed that the TEA-sensitive K+ current was the major component of action potential repolarization but that it did not effect the frequency of action potentials evoked by steady depolarization. On the other hand, blockers of Ca(2+)-sensitive K+ currents (Cd2+, Co2+, or charybdotoxin) reduced adaptation and increased the frequency of action potentials significantly but did not effect the duration or amplitude of individual action potentials.

Effects of soma isolation on outward currents measured under voltage clamp in spiny lobster stomatogastric motor neurons

1993 ◽  
Vol 69 (6) ◽  
pp. 2056-2071 ◽  
Author(s):  
D. K. Hartline ◽  
D. V. Gassie ◽  
B. R. Jones
Keyword(s):  
Voltage Clamp ◽  
Motor Neurons ◽  
Time Course ◽  
Spiny Lobster ◽  
Outward Current ◽  
Specific Conductance ◽  
Activation Threshold ◽  
Intact Cells ◽  
Mean Values ◽  
Outward Currents

1. Outward currents in identified cell types from the pyloric system of the stomatogastric ganglion (STG) of the spiny lobster, Panulirus marginatus, were studied under two-microelectrode voltage clamp. A comparison was made between data from intact cells and somata isolated by ligation of the primary neurite of these monopolar neurons. 2. Despite the elimination of current contributions from the extensive arborizations of STG neurons, few significant differences were found in the mean values of parameters for outward currents between populations of isolated somata and intact cells of a given type. Measurements that showed little difference included magnitude and activation threshold of a calcium-dependent outward current (IJ) and magnitude, activation threshold, voltage dependence, and inactivation time course of A current (IA). Although previous work has suggested that IJ might reside predominantly in the soma, IA is known to be distributed in poorly space-clamped neurite processes. The absence of obvious effects of isolation was thus unexpected. 3. To better understand the mechanisms involved, we used compartmental models derived from reconstructed neurons to simulate the effects of isolation. It was concluded that, for the particular conditions present in stomatogastric neurons, with a large, uniformly distributed outward current conductance activated, even though neurites and axon remain attached, most measured current flows through well-clamped soma membrane. 4. Factors contributing to this result included the outward sign of the current, the large specific conductance activated in these neurons (among the larger reported in somata), and the presence of only a single major process leaving the soma. The potential for serious errors in voltage-clamp measurements from intact cells remains if these conditions are not met.

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