scholarly journals Expression and function of a CP339,818-sensitive K+ current in a subpopulation of putative nociceptive neurons from adult mouse trigeminal ganglia

2015 ◽  
Vol 113 (7) ◽  
pp. 2653-2665 ◽  
Author(s):  
Luigi Sforna ◽  
Maria Cristina D'Adamo ◽  
Ilenio Servettini ◽  
Luca Guglielmi ◽  
Mauro Pessia ◽  
...  
Keyword(s):  
Steady State ◽  
Firing Frequency ◽  
Resting Potential ◽  
Trigeminal Ganglia ◽  
Nociceptive Neurons ◽  
Steady State Inactivation ◽  
Biophysical Study ◽  
K Current ◽  
Membrane Resting Potential ◽  
And Function

Trigeminal ganglion (TG) neurons are functionally and morphologically heterogeneous, and the molecular basis of this heterogeneity is still not fully understood. Here we describe experiments showing that a subpopulation of neurons expresses a delayed-rectifying K+ current ( IDRK) with a characteristically high (nanomolar) sensitivity to the dihydroquinoline CP339,818 (CP). Although submicromolar CP has previously been shown to selectively block Kv1.3 and Kv1.4 channels, the CP-sensitive IDRK found in TG neurons could not be associated with either of these two K+ channels. It could neither be associated with Kv2.1 channels homomeric or heteromerically associated with the Kv9.2, Kv9.3, or Kv6.4 subunits, whose block by CP, tested using two-electrode voltage-clamp recordings from Xenopus oocytes, resulted in the low micromolar range, nor to the Kv7 subfamily, given the lack of blocking efficacy of 3 μM XE991. Within the group of multiple-firing neurons considered in this study, the CP-sensitive IDRK was preferentially expressed in a subpopulation showing several nociceptive markers, such as small membrane capacitance, sensitivity to capsaicin, and slow afterhyperpolarization (AHP); in these neurons the CP-sensitive IDRK controls the membrane resting potential, the firing frequency, and the AHP duration. A biophysical study of the CP-sensitive IDRK indicated the presence of two kinetically distinct components: a fast deactivating component having a relatively depolarized steady-state inactivation ( IDRKf) and a slow deactivating component with a more hyperpolarized V1/2 for steady-state inactivation ( IDRKs).

Existence of a transient outward K+ current in guinea pig cardiac myocytes

2000 ◽  
Vol 279 (1) ◽  
pp. H130-H138 ◽  
Author(s):  
Gui-Rong Li ◽  
Baofeng Yang ◽  
Haiying Sun ◽  
Clive M. Baumgarten
Keyword(s):  
Guinea Pig ◽  
Ventricular Myocytes ◽  
Outward Current ◽  
Resting Potential ◽  
Transient Outward Current ◽  
Time Constants ◽  
Zero Current ◽  
Steady State Inactivation ◽  
K Current ◽  
External K

A novel transient outward K+current that exhibits inward-going rectification ( I to.ir) was identified in guinea pig atrial and ventricular myocytes. I to.ir was insensitive to 4-aminopyridine (4-AP) but was blocked by 200 μmol/l Ba2+or removal of external K+. The zero current potential shifted 51–53 mV/decade change in external K+. I to.ir density was twofold greater in ventricular than in atrial myocytes, and biexponential inactivation occurs in both types of myocytes. At −20 mV, the fast inactivation time constants were 7.7 ± 1.8 and 6.1 ± 1.2 ms and the slow inactivation time constants were 85.1 ± 14.8 and 77.3 ± 10.4 ms in ventricular and atrial cells, respectively. The midpoints for steady-state inactivation were −36.4 ± 0.3 and −51.6 ± 0.4 mV, and recovery from inactivation was rapid near the resting potential (time constants = 7.9 ± 1.9 and 8.8 ± 2.1 ms, respectively). I to.ir was detected in Na+-containing and Na+-free solutions and was not blocked by 20 nmol/l saxitoxin. Action potential clamp revealed that I to.ir contributed an outward current that activated rapidly on depolarization and inactivated by early phase 2 in both tissues. Although it is well known that 4-AP-sensitive transient outward current is absent in guinea pig, this Ba2+-sensitive and 4-AP-insensitive K+ current has been overlooked.

scholarly journals The calcium-independent transient outward potassium current in isolated ferret right ventricular myocytes. II. Closed state reverse use-dependent block by 4-aminopyridine.

1993 ◽  
Vol 101 (4) ◽  
pp. 603-626 ◽  
Author(s):  
D L Campbell ◽  
Y Qu ◽  
R L Rasmusson ◽  
H C Strauss
Keyword(s):  
Steady State ◽  
Right Ventricular ◽  
Ventricular Myocytes ◽  
Patch Clamp Technique ◽  
Time Constants ◽  
Closed State ◽  
Whole Cell Patch Clamp ◽  
Dependent Behavior ◽  
Steady State Inactivation ◽  
K Current

Block of the calcium-independent transient outward K+ current, I(to), by 4-aminopyridine (4-AP) was studied in ferret right ventricular myocytes using the whole cell patch clamp technique. 4-AP reduces I(to) through a closed state blocking mechanism displaying "reverse use-dependent" behavior that was inferred from: (a) development of tonic block at hyperpolarized potentials; (b) inhibition of development of tonic block at depolarized potentials; (c) appearance of "crossover phenomena" in which the peak current is delayed in the presence of 4-AP at depolarized potentials; (d) relief of block at depolarized potentials which is concentration dependent and parallels steady-state inactivation for low 4-AP concentrations (V1/2 approximately -10 mV in 0.1 mM 4-AP) and steady-state activation at higher concentrations (V1/2 = +7 mV in 1 mM 4-AP, +15 mV in 10 mM 4-AP); and (e) reassociation of 4-AP at hyperpolarized potentials. No evidence for interaction of 4-AP with either the open or inactivated state of the I(to) channel was obtained from measurements of kinetics of recovery and deactivation in the presence of 0.5-1.0 mM 4-AP. At hyperpolarized potentials (-30 to -90 mV) 10 mM 4-AP associates slowly (time constants ranging from approximately 800 to 1,300 ms) with the closed states of the channel (apparent Kd approximately 0.2 mM). From -90 to -20 mV the affinity of the I(to) channel for 4-AP appears to be voltage insensitive; however, at depolarized potentials (+20 to +100 mV) 4-AP dissociates with time constants ranging from approximately 350 to 150 ms. Consequently, the properties of 4-AP binding to the I(to) channel undergo a transition in the range of potentials over which channel activation and inactivation occurs (-30 to +20 mV). We propose a closed state model of I(to) channel gating and 4-AP binding kinetics, in which 4-AP binds to three closed states. In this model 4-AP has a progressively lower affinity as the channel approaches the open state, but has no intrinsic voltage dependence of binding.

scholarly journals The calcium-independent transient outward potassium current in isolated ferret right ventricular myocytes. I. Basic characterization and kinetic analysis.

1993 ◽  
Vol 101 (4) ◽  
pp. 571-601 ◽  
Author(s):  
D L Campbell ◽  
R L Rasmusson ◽  
Y Qu ◽  
H C Strauss
Keyword(s):  
Steady State ◽  
Ventricular Myocytes ◽  
Nonlinear Least Squares ◽  
Patch Clamp Technique ◽  
Time Constants ◽  
Whole Cell Patch Clamp ◽  
Voltage Dependent ◽  
Steady State Inactivation ◽  
K Current ◽  
Necessary And Sufficient

Enzymatically isolated myocytes from ferret right ventricles (12-16 wk, male) were studied using the whole cell patch clamp technique. The macroscopic properties of a transient outward K+ current I(to) were quantified. I(to) is selective for K+, with a PNa/PK of 0.082. Activation of I(to) is a voltage-dependent process, with both activation and inactivation being independent of Na+ or Ca2+ influx. Steady-state inactivation is well described by a single Boltzmann relationship (V1/2 = -13.5 mV; k = 5.6 mV). Substantial inactivation can occur during a subthreshold depolarization without any measurable macroscopic current. Both development of and recovery from inactivation are well described by single exponential processes. Ensemble averages of single I(to) channel currents recorded in cell-attached patches reproduce macroscopic I(to) and indicate that inactivation is complete at depolarized potentials. The overall inactivation/recovery time constant curve has a bell-shaped potential dependence that peaks between -10 and -20 mV, with time constants (22 degrees C) ranging from 23 ms (-90 mV) to 304 ms (-10 mV). Steady-state activation displays a sigmoidal dependence on membrane potential, with a net aggregate half-activation potential of +22.5 mV. Activation kinetics (0 to +70 mV, 22 degrees C) are rapid, with I(to) peaking in approximately 5-15 ms at +50 mV. Experiments conducted at reduced temperatures (12 degrees C) demonstrate that activation occurs with a time delay. A nonlinear least-squares analysis indicates that three closed kinetic states are necessary and sufficient to model activation. Derived time constants of activation (22 degrees C) ranged from 10 ms (+10 mV) to 2 ms (+70 mV). Within the framework of Hodgkin-Huxley formalism, Ito gating can be described using an a3i formulation.

Voltage-dependent inactivation of the potassium current of embryonic chick hepatocytes

1991 ◽  
Vol 69 (6) ◽  
pp. 739-745 ◽  
Author(s):  
Ceredwyn E. Hill ◽  
Alvin Shrier
Keyword(s):  
Steady State ◽  
Potassium Current ◽  
Time Course ◽  
Resting Potential ◽  
Embryonic Chick ◽  
Dependent Inactivation ◽  
Voltage Dependent ◽  
Open Development ◽  
Steady State Inactivation ◽  
Time Courses

The whole-cell patch electrode voltage clamp technique was used to study the inactivation properties of the delayed rectifying potassium current of single cultured embryonic chick hepatocytes at 20 °C. The potassium current activates maximally within 250–500 ms of membrane depolarization, after which it decays with a monoexponential time course. Both steady-state activation and inactivation are voltage dependent. Steady-state inactivation declines from 100% at −5 mV to 0 near −70 mV, with half inactivation at −41 mV. At the resting potential (EM) of these cells (−21.5 ± 6.0 mV, n = 36) 6–18% of the IK channels are not inactivated and less than 5% are open. Development and removal of inactivation follow single exponential time courses. The inactivation time constant attains a maximum of around 30 s at −35 mV and is sharply voltage dependent at the EM of these cells. Measurement of EM under current clamp shows random oscillations of 5–10 mV amplitude. We suggest that the voltage- and time-dependent properties of IK, in tandem with a time- and voltage-independent, nonselective current also seen here, would provide the mechanism for a fluctuating EM.Key words: hepatocyte, embryonic, potassium current.

The inactivating potassium currents of hair cells isolated from the crista ampullaris of the frog

1992 ◽  
Vol 68 (5) ◽  
pp. 1642-1653 ◽  
Author(s):  
C. H. Norris ◽  
A. J. Ricci ◽  
G. D. Housley ◽  
P. S. Guth
Keyword(s):  
Steady State ◽  
Hair Cells ◽  
Reversal Potential ◽  
Semicircular Canals ◽  
Cell Voltage ◽  
Leopard Frog ◽  
Resting Potential ◽  
Voltage Response ◽  
Calcium Dependent ◽  
Steady State Inactivation

1. A-type outward currents were studied in sensory hair cells isolated from the semicircular canals (SCC) of the leopard frog (Rana pipiens) with whole-cell voltage- and current-clamping techniques. 2. There appear to be two classes of A-type outward-conducting potassium channels based on steady-state, kinetic, pharmacological parameters, and reversal potential. 3. The two classes of A-type currents differ in their steady-state inactivation properties as well as in the kinetics of inactivation. The steady-state inactivation properties are such that a significant portion of the fast channels are available from near the resting potential. 4. The inactivating channels studied do not appear to be calcium dependent. 5. The A-channels in hair cells appear to subserve functions that are analogous to IA functions in neurons, that is, modulating spike latency and Q (the oscillatory damping function). The A-currents appear to temporally limit the hair cell voltage response to a current injection.

Transient and delayed potassium currents in the Retzius cell of the leech, Macrobdella decora

1986 ◽  
Vol 56 (3) ◽  
pp. 812-822 ◽  
Author(s):  
J. Johansen ◽  
A. L. Kleinhaus
Keyword(s):  
Steady State ◽  
Time Constant ◽  
Time Course ◽  
Substantial Part ◽  
Macrobdella Decora ◽  
Voltage Dependent ◽  
Steady State Inactivation ◽  
K Current ◽  
Retzius Cell ◽  
T Tau

The properties of a quickly inactivating transient K current (IA) and a slowly inactivating delayed K current (IK) were investigated with two-electrode voltage-clamp techniques in the isolated soma of the Retzius cell of the leech, Macrobdella decora. The two currents could be pharmacologically separated according to their different sensitivities to tetraethylammonium ions (TEA) and 4-aminopyridine (4-AP). IA was totally blocked by 3 mM 4-AP but not affected by 25 mM TEA. IK was suppressed almost completely by 25 mM TEA, whereas its peak amplitude only decreased by 10-15% in 3 mM 4-AP. IA was activated at membrane potentials more positive than -35 to -30 mV, whereas the threshold for IK was at more positive potentials of approximately -20 to -15 mV. The activation of IA was rapid with a voltage-dependent time constant [tau m(A)] that varied from 6 to 2 ms for command potentials between -20 and 10 mV (at 22-24 degrees C). The inactivation, which was independent of voltage, was somewhat slower with a time constant (tau A) of approximately 90-110 ms. The time constants for activation [tau m(K)] and the early inactivation phase (tau K) of IK were both voltage dependent. In the range of potential steps from 0 to 30 mV, tau m(K) varied from 12 to 4.5 ms and tau K from 1,500 to 700 ms. The steady-state inactivation of IA varied with holding potential and was complete at potentials more positive than -30 mV. IA was fully available from potentials more negative than -70 mV. IK did not show steady-state inactivation below its threshold of activation. The time course of IA during a maintained depolarization could be reasonably described by the expression IA(t) = IA(infinity) [1-exp(-t/tau m(A))]2 exp(-t/tau A). The time course of activation of IK without allowance for inactivation was approximated by the expression IK(t) = IK(infinity) [1-exp(-t/tau m(K))]2. The reversal potentials and magnitude of both IA and IK were dependent on extra-cellular K concentration, which suggest that a substantial part of the two currents was carried by K ions.

A fast transient potassium current in thalamic relay neurons: kinetics of activation and inactivation

1991 ◽  
Vol 66 (4) ◽  
pp. 1304-1315 ◽  
Author(s):  
J. R. Huguenard ◽  
D. A. Coulter ◽  
D. A. Prince
Keyword(s):  
Steady State ◽  
Reversal Potential ◽  
Cell Voltage ◽  
Inactivation Kinetics ◽  
Voltage Dependent ◽  
Steady State Inactivation ◽  
K Current ◽  
K Currents ◽  
Relay Neurons

1. Whole-cell voltage-clamp techniques were used to record K+ currents in relay neurons (RNs) that had been acutely isolated from rat thalamic ventrobasal complex and maintained at 23 degrees C in vitro. Tetrodoxin (TTX; 0.5 microM) was used to block Na+ currents, and reduced extracellular levels of Ca2+ (1 mM) were used to minimize contributions from Ca2+ current (ICa). 2. In RNs, depolarizing commands activate K+ currents characterized by a substantial rapidly inactivating (time constant approximately 20 ms) component, the features of which correspond to those of the transient K+ current (IA) in other preparations, and by a smaller, more slowly activating K+ current, "IK". IA was reversibly blocked by 4-aminopyridine (4-AP, 5 mM), and the reversal potential varied with [K+]o as predicted by the Nernst equation. 3. IA was relatively insensitive to blockade by tetraethylammonium [TEA; 50%-inhibitory concentration (IC50) much much greater than 20 mM]; however, two components of IK were blocked with IC50S of 30 microM and 3 mM. Because 20 mM TEA blocked 90% of the sustained current while reducing IA by less than 10%, this concentration was routinely used in experiments in which IA was isolated and characterized. To further minimize contamination by other conductances, 4-AP was added to TEA-containing solutions and the 4-AP-sensitive current was obtained by subtraction. 4. Voltage-dependent steady-state inactivation of peak IA was described by a Boltzman function with a slope factor (k) of -6.5 and half-inactivation (V1/2) occurring at -75 mV. Activation of IA was characterized by a Boltzman curve with V1/2 = -35 mV and k = 10.8. 5. IA activation and inactivation kinetics were best fitted by the Hodgkin-Huxley m4h formalism. The rate of activation was voltage dependent, with tau m decreasing from 2.3 ms at -40 mV to 0.5 ms at +50 mV. Inactivation was relatively voltage independent and nonexponential. The rate of inactivation was described by two exponential decay processes with time constants (tau h1 and tau h2) of 20 and 60 ms. Both components were steady-state inactivated with similar voltage dependence. 6. Temperature increases within the range of 23-35 degrees C caused IA activation and inactivation rates to become faster, with temperature coefficient (Q10) values averaging 2.8. IA amplitude also increased as a function of temperature, albeit with a somewhat lower Q10 of 1.6. 7. Several voltage-dependent properties of IA closely resemble those of the transient inward Ca2+ current, IT. (ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Voltage- and time-dependent K+ channel currents in the basolateral membrane of villus enterocytes isolated from guinea pig small intestine.

1994 ◽  
Vol 103 (3) ◽  
pp. 429-446 ◽  
Author(s):  
H Tatsuta ◽  
S Ueda ◽  
S Morishima ◽  
Y Okada
Keyword(s):  
Steady State ◽  
Guinea Pig ◽  
Time Course ◽  
Basolateral Membrane ◽  
Time Dependent ◽  
K Channel ◽  
Voltage Dependent ◽  
Steady State Inactivation ◽  
K Current ◽  
K Currents

Patch-clamp studies were carried out in villus enterocytes isolated from the guinea pig proximal small intestine. In the whole-cell mode, outward K+ currents were found to be activated by depolarizing command pulses to -45 mV. The activation followed fourth order kinetics. The time constant of K+ current activation was voltage-dependent, decreasing from approximately 3 ms at -10 mV to 1 ms at +50 mV. The K+ current inactivated during maintained depolarizations by a voltage-independent, monoexponential process with a time constant of approximately 470 ms. If the interpulse interval was shorter than 30 s, cumulative inactivation was observed upon repeated stimulations. The steady state inactivation was voltage-dependent over the voltage range from -70 to -30 mV with a half inactivation voltage of -46 mV. The steady state activation was also voltage-dependent with a half-activation voltage of -22 mV. The K+ current profiles were not affected by chelation of cytosolic Ca2+. The K+ current induced by a depolarizing pulse was suppressed by extracellular application of TEA+, Ba2+, 4-aminopyridine or quinine with half-maximal inhibitory concentrations of 8.9 mM, 4.6 mM, 86 microM and 26 microM, respectively. The inactivation time course was accelerated by quinine but decelerated by TEA+, when applied to the extracellular (but not the intracellular) solution. Extracellular (but not intracellular) applications of verapamil and nifedipine also quickened the inactivation time course with 50% effective concentrations of 3 and 17 microM, respectively. Quinine, verapamil and nifedipine shifted the steady state inactivation curve towards more negative potentials. Outward single K+ channel events with a unitary conductance of approximately 8.4 pS were observed in excised inside-out patches of the basolateral membrane, when the patch was depolarized to -40 mV. The ensemble current rapidly activated and thereafter slowly inactivated with similar time constants to those of whole-cell K+ currents. It is concluded that the basolateral membrane of guinea pig villus enterocytes has a voltage-gated, time-dependent, Ca(2+)-insensitive, small-conductance K+ channel. Quinine, verapamil, and nifedipine accelerate the inactivation time course by affecting the inactivation gate from the external side of the cell membrane.

scholarly journals After-hyperpolarization promotes the firing of mitral cells through a voltage dependent modification of action potential threshold

2021 ◽  
Author(s):  
Fourcaud-Trocmé Nicolas ◽  
Zbili Mickaël ◽  
Duchamp-Viret Patricia ◽  
Kuczewski Nicola
Keyword(s):  
Action Potential ◽  
Membrane Depolarization ◽  
Firing Frequency ◽  
Resting Potential ◽  
Mitral Cells ◽  
Patch Clamp Recording ◽  
Voltage Dependent ◽  
Membrane Resting Potential ◽  
Dependent Modification ◽  
Membrane Oscillations

AbstractIn the olfactory bulb (OB), mitral cells (MCs) display a spontaneous firing that is characterized by bursts of action potentials intermixed with silent periods. Burst firing frequency and duration are heterogeneous among MCs and increase with membrane depolarization. By using patch clamp recording on rat slices, we dissected out the intrinsic properties responsible of this activity. We showed that the threshold of action potential (AP) generation dynamically changes as a function of the trajectory of the membrane potential; becoming more negative when the membrane was hyperpolarized and having a recovering rate, inversely proportional to the membrane repolarization rate. Such variations appeared to be produced by changes in the inactivation state of voltage dependent Na+ channels. Thus, the modification AP threshold favours the initiation of the burst following hyperpolarizing event such as negative membrane oscillations or inhibitory transmission. After the first AP, the following afterhyperpolarization (AHP) brought the threshold just below the membrane resting potential or within membrane oscillations and, as a consequence, the threshold was exceeded during the fast repolarization component of the AHP. In this way the fast AHP acts as a regenerative mechanism that sustains the firing. Bursts were stopped by the development of a slow repolarization component of the AHP. The AHP characteristics appeared as determining the bursting properties; AHP with larger amplitudes and faster repolarizations being associated with longer and higher frequency bursts. Thus, the increase of bursts length and frequency upon membrane depolarization would be attributable to the modifications of the AHP and of Na+ channels inactivation.

Electrophysiologic Mechanism Underlying Action Potential Prolongation by Sevoflurane in Rat Ventricular Myocytes

2007 ◽  
Vol 107 (1) ◽  
pp. 67-74 ◽  
Author(s):  
Jee Eun Chae ◽  
Duck Sun Ahn ◽  
Myung Hee Kim ◽  
Carl Lynch ◽  
Wyun Kon Park
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Ventricular Myocytes ◽  
Outward Current ◽  
Inward Rectifier ◽  
Rat Ventricular Myocytes ◽  
Steady State Inactivation ◽  
K Current ◽  
Action Potential Prolongation ◽  
Sustained Outward Current

Abstract Background: Despite prolongation of the QTc interval in humans during sevoflurane anesthesia, little is known about the mechanisms that underlie these actions. In rat ventricular myocytes, the effect of sevoflurane on action potential duration and underlying electrophysiologic mechanisms were investigated. Methods: The action potential was measured by using a current clamp technique. The transient outward K+ current was recorded during depolarizing steps from −80 mV, followed by brief depolarization to −40 mV and then depolarization up to +60 mV. The voltage dependence of steady state inactivation was determined by using a standard double-pulse protocol. The sustained outward current was obtained by addition of 5 mm 4-aminopyridine. The inward rectifier K+ current was recorded from a holding potential of −40 mV before their membrane potential was changed from −130 to 0 mV. Sevoflurane actions on L-type Ca2+ current were also obtained. Results: Sevoflurane prolonged action potential duration, whereas the amplitude and resting membrane potential remained unchanged. The peak transient outward K+ current at +60 mV was reduced by 18 ± 2% (P < 0.05) and 24 ± 2% (P < 0.05) by 0.35 and 0.7 mm sevoflurane, respectively. Sevoflurane had no effect on the sustained outward current. Whereas 0.7 mm sevoflurane did not shift the steady state inactivation curve, it accelerated the current inactivation (P < 0.05). The inward rectifier K+ current at −130 mV was little altered by 0.7 mm sevoflurane. L-type Ca2+ current was reduced by 28 ± 3% (P < 0.05) and 33 ± 1% (P < 0.05) by 0.35 and 0.7 mm sevoflurane, respectively. Conclusions: Action potential prolongation by clinically relevant concentrations of sevoflurane is due to the suppression of transient outward K+ current in rat ventricular myocytes.

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