scholarly journals Dynorphin reduces calcium-dependent action potential duration by decreasing voltage-dependent calcium conductance

1984 ◽  
Vol 46 (2) ◽  
pp. 185-190 ◽  
Author(s):  
Mary Ann Werz ◽  
Robert L. Macdonald
1987 ◽  
Vol 58 (6) ◽  
pp. 1468-1484 ◽  
Author(s):  
J. Johansen ◽  
J. Yang ◽  
A. L. Kleinhaus

1. The purely calcium-dependent action potential of the anterior lateral giant (ALG) cell in the leech Haementeria was examined under voltage clamp. 2. Analysis with ion substitutions showed that the ALG cell action potential is generated by only two time- and voltage-dependent conductance systems, an inward Ca-dependent current (ICa) and an outward Ca-dependent K current IK(Ca). 3. The kinetic properties of the inward current were examined both in Cs-loaded neurons with Ca as the current carrier as well as in Ba-containing Ringer solutions with Ba as the current carrier, since Ba effectively blocked all time- and voltage-dependent outward current. 4. During a maintained depolarization, Ba and Ca currents activated with a time constant tau m, they then inactivated with the decay following a single exponential time course with a time constant tau h. The time constants for decay of both Ba and Ca currents were comparable, suggesting that the mechanism of inactivation of ICa in the ALG cell is largely voltage dependent. In the range of potentials from 5 to 45 mV, tau m varied from 8 to 2 ms and tau h varied from 250 to 125 ms. 5. The activation of currents carried by Ba, after correction for inactivation, could be described reasonably well by the expression I'Ba = I'Ba(infinity) [1--exp(-t/tau m)]. 6. The steady-state activation of the Ba-conductance mBa(infinity) increased sigmoidally with voltage and was approximated by the equation mBa(infinity) = (1 + exp[(Vh-6)/3])-1. The steady-state inactivation hBa(infinity) varied with holding potential and could be described by the equation hBa(infinity) = [1 + exp(Vh + 10/7)]-1. Recovery from inactivation of IBa was best described by the sum of two exponential time courses with time constants of 300 ms and 1.75 s, respectively. 7. The outward current IK(Ca) developed very slowly (0.5–1 s to half-maximal amplitude) and did not inactivate during a 20-s depolarizing command pulse. Tail current decay of IK(Ca) followed a single exponential time course with voltage-dependent time constants of between 360 and 960 ms. The steady-state activation n infinity of IK(Ca) increased sigmoidally with depolarization as described by the equation n infinity = [1 + exp(Vh-13.5)/-8)]-1. 8. The reversal potentials of IK(Ca) tail currents were close to the expected equilibrium potential for potassium and they varied linearly with log [K]o with a slope of 51 mV. These results suggest a high selectivity of the conductance for K ions.(ABSTRACT TRUNCATED AT 400 WORDS)


2004 ◽  
Vol 92 (2) ◽  
pp. 1105-1115 ◽  
Author(s):  
Rosie Dawkins ◽  
William F. Sewell

One feature of neuronal discharge proposed to play a role in coding temporal information is the relative refractory period that follows each action potential. In neurons innervating hair cells, there is an extended refractory period that can last ≤100 ms. We have taken a pharmacological approach to examine the extended refractory period in the Xenopus lateral line organ. We show that each action potential in the afferent fiber, whether generated spontaneously or through an antidromic electrical pulse, decreases the probability of subsequent afferent discharge for a period of ≤100 ms. We show that the extended refractory period can be modulated with drugs that alter glutamatergic transmission between the hair cell and the afferent fiber. The extended refractory period can be enhanced by perfusion with agents that reduce synaptic activity. These agents include blockers of voltage-dependent transmitter release, such as cobalt, as well as glutamate receptor antagonists, such as CNQX and kynurenic acid. Conversely, perfusion with agents that increase synaptic activity through activation of the glutamate receptors, such as AMPA or kainate, reduces the magnitude of suppression during the extended refractory period. The extended refractory period is greatly reduced by iberiotoxin and tetraethylammonium (TEA), indicating it may be mediated in large part by a calcium-dependent potassium channel. The ability to modulate the extended refractory period with changes in synaptic input suggests a simple, dynamic mechanism by which strong input (i.e., large or frequent excitatory postsynaptic potentials) can be strengthened and weak inputs weakened.


1999 ◽  
Vol 81 (1) ◽  
pp. 288-298 ◽  
Author(s):  
Jing Qian ◽  
Peter Saggau

Qian, Jing and Peter Saggau. Modulation of transmitter release by action potential duration at the hippocampal CA3-CA1 synapse. J. Neurophysiol. 81: 288–298, 1999. Presynaptic Ca2+ influx through voltage-dependent Ca2+ channels triggers neurotransmitter release. Action potential duration plays a determinant role in the dynamics of presynaptic Ca2+ influx. In this study, the presynaptic Ca2+ influx was optically measured with a low-affinity Ca2+ indicator (Furaptra). The effect of action potential duration on Ca2+ influx and transmitter release was investigated. The K+ channel blocker 4-aminopyridine (4-AP) was applied to broaden the action potential and thereby increase presynaptic Ca2+ influx. This increase of Ca2+ influx appeared to be much less effective in enhancing transmitter release than raising the extracellular Ca2+ concentration. 4-AP did not change the Ca2+ dependence of transmitter release but instead shifted the synaptic transmission curve toward larger total Ca2+ influx. These results suggest that changing the duration of Ca2+ influx is not equivalent to changing its amplitude in locally building up an effective Ca2+ concentration near the Ca2+ sensor of the release machinery. Furthermore, in the presence of 4-AP, the N-type Ca2+ channel blocker ωCgTx GVIA was much less effective in blocking transmitter release. This phenomenon was not simply due to a saturation of the release machinery by the increased overall Ca2+ influx because a similar reduction of Ca2+ influx by application of the nonspecific Ca2+ channel blocker Cd2+ resulted in much more inhibition of transmitter release. Rather, the different potencies of ω-CgTx GVIA and Cd2+ in inhibiting transmitter release suggest that the Ca2+ sensor is possibly located at a distance from a cluster of Ca2+ channels such that it is sensitive to the location of Ca2+ channels within the cluster.


1997 ◽  
Vol 77 (1) ◽  
pp. 260-271 ◽  
Author(s):  
H. Widmer ◽  
H. Amerdeil ◽  
P. Fontanaud ◽  
M. G. Desarménien

Widmer, H., H. Amerdeil, P. Fontanaud, and M. G. Desarménien. Postnatal maturation of rat hypothalamoneurohypophysial neurons: evidence for a developmental decrease in calcium entry during action potentials. J. Neurophysiol. 77: 260–271, 1997. Action potentials and voltage-gated currents were studied in acutely dissociated neurosecretory cells from the rat supraoptic nucleus during the first three postnatal weeks (PW1–PW3), a period corresponding to the final establishment of neuroendocrine relationships. Action potential duration (at half maximum) decreased from 2.7 to 1.8 ms; this was attributable to a decrease in decay time. Application of cadmium (250 μM) reduced the decay time by 43% at PW1 and 21% at PW3, indicating that the contribution of calcium currents to action potentials decreased during postnatal development. The density of high-voltage-activated calcium currents increased from 4.4 to 10.1 pA/pF at postnatal days 1–5 and 11–14, respectively. The conductance density of sustained potassium current, measured at +20 mV, increased from 0.35 (PW1) to 0.53 (PW3) nS/pF. The time to half-maximal amplitude did not change. Conductance density and time- and voltage-dependent inactivation of the transient potassium current were stable from birth. At PW1, the density and time constant of decay (measured at 0 mV) were 0.29 nS/pF ( n = 12) and 17.9 ms ( n = 10), respectively. Voltage-dependent properties and density (1.1 nS/pF) of the sodium current did not change postnatally. During PW1, fitting the mean activation data with a Boltzmann function gave a half-activation potential of −25 mV. A double Boltzman equation was necessary to adequately fit the inactivation data, suggesting the presence of two populations of sodium channels. One population accounted for ∼14% of the channels, with a half-inactivation potential of −86 mV; the remaining population showed a half-inactivation potential of −51 mV. A mathematical model, based on Hodgkin-Huxley equations, was used to assess the respective contributions of individual currents to the action potential. When the densities of calcium and sustained potassium currents were changed from immature to mature values, the decay time of the action potentials generated with the model decreased from 2.85 to 1.95 ms. A similar reduction was obtained when only the density of the potassium current was increased. Integration of the calcium currents generated during mature and immature action potentials demonstrated a significant decrease in calcium entry during development. We conclude that the developmental reduction of the action potential duration 1) is a consequence of the developmentally regulated increase in a sustained potassium current and 2) leads to a reduction of the participation of calcium currents in the action potential, resulting in a decreased amount of calcium entering the cell during each action potential.


1989 ◽  
Vol 145 (1) ◽  
pp. 395-402
Author(s):  
PAULO S. BEIRÃO ◽  
JOSÉ HAMILTON M. NASCIMENTO

The secretory epithehum of the mantle of the clam Anomalocardia brasiliana is excitable. The ionic dependence of its action potentials was investigated. Two distinct phases could be recognized by their ionic dependences. The early spike phase, that appeared in all action potentials, was dependent on the Na+ concentration of the solution in the interstitial space and was insensitive to tetrodotoxin (TTX) at concentrations as high as 36μmol l−1. It was inhibited by local anesthetics, and its repolarization was inhibited by veratrine. The data show this electrogenesis is caused by TTX-insensitive sodium channels located at the basolateral membrane of this epithelium. Cardiac-like action potentials were recorded in several specimens: the rapid Na+-dependent spike was followed by a slower repolarization phase that formed a plateau and increased the action potential duration. The plateau amplitude was markedly increased when the external Ca2+ concentration was increased to (60 mmol l−1 and it was inhibited by the addition of inorganic calcium channel blockers such as Mn2+ and Cd2+. These observations suggest that inward Ca2+ currents cause the sustained depolarization during the plateau.


1994 ◽  
Vol 71 (1) ◽  
pp. 129-145 ◽  
Author(s):  
S. H. Chandler ◽  
C. F. Hsaio ◽  
T. Inoue ◽  
L. J. Goldberg

1. Intracellular recording and stimulation were made from guinea pig trigeminal motoneurons (TMNs) in brain stem slices. Electrophysiological properties were examined and the underlying currents responsible for motoneuron excitability were investigated by the use of current clamp and single electrode voltage clamp (SEVC) techniques. 2. The voltage responses to subthreshold hyperpolarizing or depolarizing current pulses showed voltage- and time-dependent inward rectification. SEVC analysis demonstrated that the hyperpolarizing inward rectification resulted from the development of a slowly occurring voltage-dependent inward current activated at hyperpolarized membrane potentials. This current persisted in solutions containing low Ca2+/Mn2+, tetraethylammonium (TEA), and Ba2+, whereas it was reduced by 1–3 mM cesium. The depolarizing inward rectification was mediated by a persistent sodium current (INa-P) that was completely abolished by bath application of tetrodotoxin (TTX). 3. Action potential characteristics were studied by intracellular stimulation with brief current pulses (< 3 ms) in combination with ionic substitutions or application of specific ionic conductance blocking agents. Bath application of TTX abolished the action potential, whereas 1–10 mM TEA or 0.5–2 mM 4-aminopyridine (4-AP) increased, significantly, the spike duration, suggesting participation of the delayed rectifier and A-current type conductances in spike repolarization. SEVC analysis revealed a TEA-sensitive sustained outward current and a fast, voltage-dependent, transient current with properties consistent with their roles in spike repolarization. 4. TMN afterhyperpolarizing potentials (AHPs) that followed a single spike consisted of fast and slow components usually separated by a depolarizing hump [afterdepolarization (ADP)]. The fast component was abolished by TEA or 4-AP but not by Mn2+, Co2+, or the bee venom apamin. In contrast, the slow AHP was readily reduced by Mn2+, Co2+, or apamin, suggesting participation of an apamin-sensitive, calcium-dependent K+ conductance in the production of the slow AHP. SEVC analysis and ionic substitutions demonstrated a slowly activating and deactivating calcium-dependent K+ current with properties that could account for the slow AHP observed in these neurons. 5. Repetitive discharge was examined with long depolarizing current pulses (1 s) and analysis of frequency-current plots. When evoked from resting potential (about -55 mV), spike onset from rheobase occurred rapidly and was maintained throughout the current pulse. At higher current intensities, early and late adaptations in spike discharge were observed. Frequency-current plots exhibited a bilinear relationship for the first interspike interval (ISI) in approximately 50% of the neurons tested and in most neurons tested during steady-state discharge (SS).(ABSTRACT TRUNCATED AT 400 WORDS)


2000 ◽  
Vol 41 (4) ◽  
pp. 481-492
Author(s):  
Naohiko Takahashi ◽  
Morio Ito ◽  
Shuji Ishida ◽  
Takao Fujino ◽  
Mikiko Nakagawa ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document