KINETICS AND VOLTAGE DEPENDENCE OF CALCIUM INWARD CURRENT IN THE MEMBRANE OF MOLLUSC NEURONS

1981 ◽  
pp. 45-51
Author(s):  
O.A. kryshtal ◽  
P.G. Kostyuk ◽  
V.I. Pidoplichko
Keyword(s):  
Voltage Dependence ◽  
Inward Current ◽  
Calcium Inward Current ◽  
Mollusc Neurons

Dopamine modulation of two subthreshold currents produces phase shifts in activity of an identified motoneuron

1995 ◽  
Vol 74 (4) ◽  
pp. 1404-1420 ◽  
Author(s):  
R. M. Harris-Warrick ◽  
L. M. Coniglio ◽  
R. M. Levini ◽  
S. Gueron ◽  
J. Guckenheimer
Keyword(s):  
Action Potentials ◽  
Voltage Dependence ◽  
Motor Pattern ◽  
Outward Current ◽  
Untreated Cell ◽  
Slight Reduction ◽  
Inward Current ◽  
Postinhibitory Rebound ◽  
Spike Latency ◽  
Dopamine Modulation

1. The lateral pyloric (LP) neuron is a component of the 14-neuron pyloric central pattern generator in the stomatogastric ganglion of the spiny lobster, Panulirus interruptus. In the pyloric rhythm, this neuron fires rhythmic bursts of action potentials whose phasing depends on the pattern of synaptic inhibition from other network neurons and on the intrinsic postinhibitory rebound properties of the LP cell itself. Bath-applied dopamine excites the LP cell and causes its activity to be phase advanced in the pyloric motor pattern. At least part of this modulatory effect is due to dopaminergic modulation of the intrinsic rate of postinhibitory rebound in the LP cell. 2. The LP neuron was isolated from all detectable synaptic input. We measured the rate of recovery after 1-s hyperpolarizing current injections of varying amplitudes, quantifying the latency to the first spike following the hyperpolarizing prepulse and the interval between the first and second action potentials. Dopamine reduced both the first spike latency and the first interspike interval (ISI) in the isolated LP neuron. During the hyperpolarizating pre-steps, the LP cell showed a slow depolarizing sag voltage that was enhanced by dopamine. 3. We used voltage clamp to analyze dopamine modulation of subthreshold ionic currents whose activity is affected by hyperpolarizing prepulses. Dopamine modulated the transient potassium current IA by reducing its maximal conductance and shifting its voltage dependence for activation and inactivation to more depolarized voltages. This outward current is normally transiently activated after hyperpolarization of the LP cell, and delays the rate of postinhibitory rebound; by reducing IA, dopamine thus accelerates the rate of rebound of the LP neuron. 4. Dopamine also modulated the hyperpolarization-activated inward current Ih by shifting its voltage dependence for activation 20 mV in the depolarizing direction and accelerating its rate of activation. This enhanced inward current helps accelerate the rate of rebound in the LP cell after inhibition. 5. The relative roles of Ih and IA in determining the first spike latency and first ISI were explored using pharmacological blockers of Ih (Cs+) and IA [4-aminopyridine (4-AP)]. Blockade of Ih prolonged the first spike latency and first ISI, but only slightly reduced the net effect of dopamine. In the continued presence of Cs+, blockade of IA with 4-AP greatly shortened the first spike latency and first ISI. Under conditions where both Ih and IA were blocked, dopamine had no additional effect on the LP cell. 6. We used the dynamic clamp technique to further study the relative roles of IA and Ih modulation in dopamine's phase advance of the LP cell. We blocked the endogenous Ih with Cs+ and replaced it with a simulated current generated by a computer model of Ih. The neuron with simulated Ih gave curves relating the hyperpolarizing prepulse amplitude to first spike latency that were the same as in the untreated cell. Changing the computer parameters of the simulated Ih to those induced by dopamine without changing IA caused only a slight reduction in first spike latency, which was approximately 20% of the total reduction caused by dopamine in an untreated cell. Bath application of dopamine in the presence of Cs+ and simulated Ih (with control parameters) allowed us to determine the effect of altering IA but not Ih: this caused a significant reduction in first spike latency, but it was still only approximately 70% of the effect of dopamine in the untreated cell. Finally, in the continued presence of dopamine, changing the parameters of the simulated Ih to those observed with dopamine reduced the first spike latency to that seen with dopamine in the untreated cell. 7. We generated a mathematical model of the lobster LP neuron, based on the model of Buchholtz et al. for the crab LP neuron.

Analysis of catecholamine effects in single atrial trabeculae of the frog heart

1977 ◽  
Vol 197 (1128) ◽  
pp. 333-362 ◽  
Keyword(s):  
Cell Membrane ◽  
Action Potential ◽  
Time Course ◽  
Drug Exposure ◽  
Drug Application ◽  
Latency Period ◽  
Frog Heart ◽  
Phosphodiesterase Activity ◽  
Inward Current ◽  
Calcium Inward Current

A study was made of the time course of the effects of adrenaline and isoprenaline on both twitch tension and the intracellular action potential of single atrial trabeculae from frog heart, under a variety of experimental conditions. Twitch tension and overshoot of action potentials rose and subsided in a parallel fashion during build-up and decline of catecholamine action. Cessation of stimulation during drug application had little effect on the tension responses to the drugs. These, and also results obtained with step changes of external calcium concentration during drug exposure, suggest that tension enhancement is a direct consequence of the increased calcium inward current produced by the catecholamines. Exceptional results from trabeculae of ‘hypodynamic’ hearts are described and interpreted on the basis of previous findings obtained in the ‘hypo-dynamic’ condition. Under suitable conditions, including the use of brief periods of drug exposure (≤20 s), three phases of ( β -catecholamine action were discernible: (1) a latency period, of up to 15 s, which preceded tension and potential rise after drug application. Results are presented suggesting that this latency mainly reflects the time which it takes for drug-combined receptors to activate adenylate cyclase in the cell membrane. (2) A sub­sequent phase was critically dependent, in both its magnitude and time course, on phosphodiesterase activity, as was shown by the application of the specific inhibitors papaverine, ICI 63 197, and Ro 20-1724. This phase is probably controlled by the build-up and decline of cAMP within the cells and the subsequent activation and deactivation of a protein kinase. (3) A third phase, associated with the final portion of the decline of catecholamine action, was relatively insensitive to moderate inhi­bition of phosphodiesterase activity. It is attributed to a change of phosphorylation of sites at the internal surface of the cell membrane, the process which, it is assumed, determines the size of calcium inward current during an action potential. Tension decline after a short staircase occurred with a time course closely similar to that of the final phase of the declining catecholamine response. A common final step in the sequential cellular processes under­ lying the two responses is proposed. In some 40% of the trabeculae examined, adrenaline responses were of ‘mixed’ origin: in addition to the relatively slow β -adrenergic action, an initial rapid tension change was present, and experimental tests suggest that this is mediated by α -type receptors.

Characteristics and postnatal development of a hyperpolarization-activated inward current in rat hypoglossal motoneurons in vitro

1994 ◽  
Vol 71 (1) ◽  
pp. 119-128 ◽  
Author(s):  
D. A. Bayliss ◽  
F. Viana ◽  
M. C. Bellingham ◽  
A. J. Berger
Keyword(s):  
Postnatal Development ◽  
Voltage Dependence ◽  
Reversal Potential ◽  
Membrane Potentials ◽  
Time Constants ◽  
Inward Current ◽  
Hypoglossal Motoneurons ◽  
Tail Current ◽  
Cationic Current ◽  
Voltage Dependent

1. Single-electrode voltage clamp recordings in a rat brain stem slice preparation were used to determine the characteristics and postnatal development of a hyperpolarization-activated inward current (Ih) in hypoglossal motoneurons (HMs). 2. In young adult HMs (> P21), a noninactivating, time- and voltage-dependent inward current was evident during hyperpolarizing voltage steps to membrane potentials negative to approximately -65 mV from depolarized holding potentials [Vh = -56.2 +/- 1.0 (SE) mV]. The averaged reversal potential (Erev) of the inward current, estimated using an extrapolation procedure, was -38.8 +/- 2.9 mV (n = 5), suggesting that a mixed cationic current underlies inward rectification in HMs. 3. The voltage dependence of Ih activation was determined from tail current relaxations that followed a family of voltage steps to different membrane potentials. Normalized tail current amplitudes were well-fitted with a single Boltzman function with a half-activation at -79.8 +/- 0.7 mV and slope factor = 5.3 +/- 0.3 (n = 8). 4. Time constants of Ih activation and deactivation were voltage-dependent. Activation proceeded more quickly with larger hyperpolarizing voltage steps; time constants averaged 389, 181, and 134 ms at -69, -82, and -95 mV, respectively (n = 6). Ih deactivated during depolarizing voltage steps from hyperpolarized holding potentials. Deactivation was faster with larger depolarizing steps; time constants averaged 321, 215, and 107 ms at -80, -71, and -62 mV, respectively (n = 4). 5. Ih was sensitive to extracellular cesium but relatively insensitive to extracellular barium. The current amplitude near half-activation (approximately -84 mV) was almost completely blocked (to 11% of control) by Cs+ (3 mM, n = 3) but was reduced to only 85 and 60% in 0.5 (n = 2) and 2 mM Ba2+ (n = 3), respectively. 6. There was a marked increase in the amplitude of Ih during postnatal development of HMs. Measured near half-activation, Ih was approximately 10-fold larger in adult (> or = P21; n = 20) than in neonatal HMs (< or = P8; n = 7). Input conductance (GN) was only threefold higher in the same sample of HMs. There were no apparent differences in the voltage dependence or Erev of Ih between neonatal and older HMs. These results suggest that the increased amplitude of Ih results from an increase in Ih current density.(ABSTRACT TRUNCATED AT 400 WORDS)

The effect of D600 on tonic tension, Na+ inward current, and Na+–Ca2+ exchange in frog heart

1985 ◽  
Vol 63 (11) ◽  
pp. 1404-1410 ◽  
Author(s):  
Magda Horackova
Keyword(s):  
Calcium Channel ◽  
Positive Inotropic Effect ◽  
Channel Blocker ◽  
High Amplitude ◽  
Inhibitory Effect ◽  
Frog Heart ◽  
Tonic Component ◽  
Inward Current ◽  
Tonic Tension ◽  
Calcium Inward Current

Preparations of frog atrial muscle were stimulated at 0.33 Hz under voltage clamp, and the resulting membrane currents and the twitch contractions (phasic and tonic components) were recorded in presence or absence of D600. It has been suggested earlier that the tonic contractions are regulated by an electrogenic Na+–Ca2+ exchange, while the phasic contractions are closely related to the calcium inward current (Isi). In this study we investigated the effect of D600 on (i) the tonic contractions elicited by long depolarizing pulses of high amplitude and (ii) the tonic contractions increased by veratrine and resulting in a positive inotropic effect (PIE). While 1 μM D600 reduced Isi and the corresponding phasic contractions to < 30% of their initial values within 5 min, the inhibitory effect of D600 on tonic contractions developed more slowly or higher concentrations of D600 were needed to achieve similar levels of inhibition within the same time. Furthermore, applications of 5–50 μM D600 inhibited the veratrine-induced increase in INa and in tonic contractions, and both of these effects again fully developed within a few minutes of D600 being removed. The results demonstrate that D600 inhibits not only Isi and phasic contractions, but it also decreases the tonic contractions in frog heart. The effect on the tonic component is associated with inhibition of the tetrodotoxin-sensitive Na+ inward current, and the results are interpreted as an effect of D600 on the electrogenic Na+–Ca2+ exchange. These additional effects of D600 should be considered when using this drug as the "specific" calcium channel blocker.

Analysis of voltage-dependent membrane currents in spatially extended neurons from point-clamp data

1993 ◽  
Vol 69 (1) ◽  
pp. 241-247 ◽  
Author(s):  
W. Muller ◽  
H. D. Lux
Keyword(s):  
Voltage Dependence ◽  
Outward Current ◽  
Resting Potential ◽  
Inward Current ◽  
Outward Currents ◽  
Current Voltage ◽  
Voltage Dependent ◽  
Spatially Extended ◽  
Model Cell ◽  
Space Constant

1. Numerical methods were used to evaluate voltage space-clamp performance in the investigation of a voltage-dependent inward current similar to the noninactivating Ca current. In addition, the cell is equipped with a repolarizing system, represented by leak and outwardly rectifying outward conductances. The electrotonically compact model cell is represented by a cable with an electrotonic length of 1 space constant under control conditions, but that becomes effectively only 0.33 space constants during a 90% reduction of the leak and outward conductance. The cable is perfectly voltage clamped at one end. 2. The apparent voltage dependence, activation, and inactivation of the clamp current depend on the distribution of the membrane slope conductance along the cable; this depends on 1) the distribution of the inward current along the cable and 2) the amplitude of the inward current relative to the amplitudes of the leak and voltage-dependent outward currents. 3. Under control conditions, the membrane voltage decays steeply with distance from the command voltage at the clamp site to almost resting potential for most of the rest of the cable. This is because the leak and outward current are dominant over the inward current. The inward current is activated primarily at the clamped part of the cable. Clamp currents are activated instantaneously. The clamp-current current-voltage (I-V) relation is less steep with depolarization because the membrane potential for locations away from the clamp site lags behind the clamp potential. 4. When the conductances for leak and outward current are reduced by 90%, these conductances lose their dominance. The membrane slope conductance now has a range with negative values.(ABSTRACT TRUNCATED AT 250 WORDS)

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