Activation and Deactivation of Voltage-Dependent K+ Channels During Synaptically Driven Action Potentials in the MNTB

2006 ◽  
Vol 96 (3) ◽  
pp. 1547-1555 ◽  
Author(s):  
Achim Klug ◽  
Laurence O. Trussell
Keyword(s):  
Action Potentials ◽  
Time Course ◽  
Low Voltage ◽  
Multiple Roles ◽  
Synaptic Activity ◽  
Leak Current ◽  
Medial Nucleus ◽  
Voltage Dependent ◽  
Spike Waveforms ◽  
Trapezoid Body

K+ channels shape individual action potentials and determine their pattern of firing. In auditory relays, both high- and low-voltage–activated K+ channels (HVA and LVA) are critical for preservation of auditory timing cues. We examined how these channels participate in firing in the medial nucleus of the trapezoid body. Principal cells at physiological temperature were voltage clamped using spike waveforms previously recorded in response to calyceal firing. Current components were isolated by digital subtraction of traces recorded in the channel antagonists dendrotoxin-I or tetraethylammonium. During orthodromic spikes delivered at 300 and 600 Hz, both currents activated with a slight delay, peaking just after the crest of the spike. The decay of HVA was sufficiently fast to match the time course of the spike. By contrast, with 300-Hz stimuli, LVA continued to decay after the spikes reached a stable interspike potential. Although LVA currents partially inactivate during prolonged voltage steps, their peak amplitudes remained stable or increased during trains of spikelike stimuli. At 600 Hz, LVA did not fully deactivate between the spikes and therefore generated a leak current. To determine the effect of blocking LVA channels on spiking, prerecorded postsynaptic conductances were injected, with and without dendrotoxin-I. After block of LVA channels, strong synaptic conductances produced broader spikes, greater spike jitter, and prolonged depolarized states. HVA blockade with tetraethylammonium also broadened spikes but led to less error in timing. These results reveal multiple roles for LVA channels in spike repolarization and timing during synaptic activity.

Seizures and Reduced Life Span in Mice Lacking the Potassium Channel Subunit Kv1.2, but Hypoexcitability and Enlarged Kv1 Currents in Auditory Neurons

2007 ◽  
Vol 98 (3) ◽  
pp. 1501-1525 ◽  
Author(s):  
Helen M. Brew ◽  
Joshua X. Gittelman ◽  
Robert S. Silverstein ◽  
Timothy D. Hanks ◽  
Vas P. Demas ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Low Voltage ◽  
Seizure Susceptibility ◽  
Auditory Neurons ◽  
Medial Nucleus ◽  
Voltage Dependent ◽  
Similar Phenotype ◽  
Brain Stem Slices ◽  
Trapezoid Body ◽  
Fine Tune

Genes Kcna1 and Kcna2 code for the voltage-dependent potassium channel subunits Kv1.1 and Kv1.2, which are coexpressed in large axons and commonly present within the same tetramers. Both contribute to the low-voltage–activated potassium current IKv1, which powerfully limits excitability and facilitates temporally precise transmission of information, e.g., in auditory neurons of the medial nucleus of the trapezoid body (MNTB). Kcna1-null mice lacking Kv1.1 exhibited seizure susceptibility and hyperexcitability in axons and MNTB neurons, which also had reduced IKv1. To explore whether a lack of Kv1.2 would cause a similar phenotype, we created and characterized Kcna2-null mice (−/−). The −/− mice exhibited increased seizure susceptibility compared with their +/+ and +/− littermates, as early as P14. The mRNA for Kv1.1 and Kv1.2 increased strongly in +/+ brain stems between P7 and P14, suggesting the increasing importance of these subunits for limiting excitability. Surprisingly, MNTB neurons in brain stem slices from −/− and +/− mice were hypoexcitable despite their Kcna2 deficit, and voltage-clamped −/− MNTB neurons had enlarged IKv1. This contrasts strikingly with the Kcna1-null MNTB phenotype. Toxin block experiments on MNTB neurons suggested Kv1.2 was present in every +/+ Kv1 channel, about 60% of +/− Kv1 channels, and no −/− Kv1 channels. Kv1 channels lacking Kv1.2 activated at abnormally negative potentials, which may explain why MNTB neurons with larger proportions of such channels had larger IKv1. If channel voltage dependence is determined by how many Kv1.2 subunits each contains, neurons might be able to fine-tune their excitability by adjusting the Kv1.1:Kv1.2 balance rather than altering Kv1 channel density.

Kinetic and pharmacological properties of low voltage-activated Ca2+ current in rat clonal (GH3) pituitary cells

1992 ◽  
Vol 68 (1) ◽  
pp. 213-232 ◽  
Author(s):  
J. Herrington ◽  
C. J. Lingle
Keyword(s):  
Time Course ◽  
Low Voltage ◽  
Gh3 Cells ◽  
Pituitary Cells ◽  
Anesthetic Agents ◽  
Channel Opening ◽  
Cell Recording ◽  
Voltage Dependent ◽  
Dependent Processes ◽  
Site Binding

1. Low voltage-activated (LVA) Ca2+ current in clonal (GH3) pituitary cells was studied with the use of the whole-cell recording technique. The use of internal fluoride to facilitate the rundown of high voltage-activated (HVA) Ca2+ current allowed the study of LVA current in virtual isolation. 2. In 10 mM [Ca2+]o, detectable LVA current begins to appear at about -50 mV, with half-maximal activation occurring at -33 mV. The time course of activation was best described by a Hodgkin-Huxley expression with n = 3, suggesting that at least three closed states must be traversed before channel opening. 3. Deactivation was found to vary exponentially with membrane potential between -60 and -160 mV, indicating that channel closing is rate-limited by a single, voltage-dependent transition. 4. Onset and removal of inactivation between -40 and -130 mV were best described by the sum of two exponentials. Between -80 and -130 mV, both components of removal of inactivation showed little voltage dependence, with time constants of approximately 200-300 ms and 1-2 s. At membrane potentials above -40 mV, a single component of inactivation onset was detected. This component was voltage independent between -20 and +20 mV (tau = 22 ms). Thus inactivation of LVA current is best described by multiple, voltage-in-dependent processes. 5. Significant inactivation of LVA current occurred at -65 mV without detectable macroscopic current. This suggests that inactivation is not strictly coupled to channel opening. 6. Peak LVA current increased with increasing [Ca2+]o, with saturation approximately 50 mM. The Ca(2+)-dependence of peak LVA current was reasonably well described by a single-site binding isotherm with half-maximal LVA current at approximately 7 mM. 7. LVA current in GH3 cells was largely resistant to blockade by Ni2+. The relative potency of inorganic cations in blocking GH3 LVA current was (concentrations which produced 50% block): La3+ (2.4 microM) greater than Cd2+ (188 microM) greater than Ni2+ (777 microM). 8. Several organic agents, including putative LVA blockers, HVA current blockers and various anesthetic agents, were tested for their ability to block LVA current. The concentrations that produced 50% block are as follows: nifedipine (approximately 50 microM), D600 (51 microM), diltiazem (131 microM), octanol (244 microM), pentobarbital (985 microM), methoxyflurane (1.41 mM), and amiloride (1.55 mM). Phenytoin and ethosuximide produced 36 and 10% block at 100 microM and 2.5 mM, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Role of Ca2+ in the Synchronization of Transmitter Release at Calyceal Synapses in the Auditory System of Rat

2002 ◽  
Vol 87 (1) ◽  
pp. 222-228 ◽  
Author(s):  
Nao Chuhma ◽  
Harunori Ohmori
Keyword(s):  
Transmitter Release ◽  
Time Course ◽  
Presynaptic Terminal ◽  
Eosin Y ◽  
Early Postnatal Development ◽  
Medial Nucleus ◽  
Combined Application ◽  
Asynchronous Release ◽  
Trapezoid Body

The synchronization of transmitter release in the synapse of the medial nucleus of the trapezoid body (MNTB) is achieved during early postnatal development as a consequence of elimination of delayed asynchronous releases and appears to reflect changes in the dynamics of Ca2+ entry and clearance. To examine the role of Ca2+ in regulating synchronization of transmitter release in the mature synapse (after postnatal day 9, P9), we perturbed Ca2+ dynamics systematically. Replacement of external Ca2+ (2 mM) with Sr2+ induced delayed asynchronous release following the major EPSC. We tried to reproduce asynchronous releases without using Sr2+ and instead by manipulating the time course and the size of Ca2+ transient in the presynaptic terminal, under the assumption that replacement of external Na+ with Li+ or application of eosin-Y would prolong the lifetime of Ca2+ transient by reducing the rate of Ca2+ extrusion from the terminal. With application of Li+, Ca2+ transient in the terminal was prolonged, the EPSC decay time course was prolonged, and the EPSC amplitude increased. However, these EPSCs were not followed by delayed asynchronous release. When Ca2+ influx was reduced, either by partial Ca2+ channel blockade with a low concentration of Cd2+ or ω-agatoxin IVA, a marked asynchronous release resulted. This was further enhanced by the combined application of Li+ or eosin-Y. These results suggest that cooperative increases of both Ca2+ influx and Ca2+ clearance capacities leading to a sharper Ca2+ spike in the presynaptic terminal underlie synchronized transmitter release in the presynaptic terminal of the MNTB.

Low-voltage activated calcium currents increase in basal forebrain neurons from aged rats

1995 ◽  
Vol 74 (2) ◽  
pp. 876-887 ◽  
Author(s):  
D. Murchison ◽  
W. H. Griffith
Keyword(s):  
Time Course ◽  
Low Voltage ◽  
Age Groups ◽  
Medial Septum ◽  
Calcium Currents ◽  
Fischer 344 ◽  
Diagonal Band ◽  
Whole Cell Patch Clamp ◽  
Age Related ◽  
Voltage Dependent

1. Whole cell patch-clamp recordings were made of low-voltage-activated (LVA) calcium (Ca2+) currents using 2 mM barium (Ba2+) as charge carrier. Acutely dissociated neurons from medial septum (MS) and the nucleus of the diagonal band (nDB) were examined in young adult (1–3 mo) and aged (24–26 mo) Fischer 344 rats. 2. Most neurons in both age groups displayed LVA currents: 84% of young cells (110/131) and 87% in aged cells (62/71). Using cell capacitance as an indication of cell size, aged cells were significantly smaller (P < 0.05; 15.4 +/- 0.6 pF; mean +/- SE) than young cells (18.0 +/- 0.5 pF), although a single distribution of cell sizes was present in both populations. 3. The LVA currents were enhanced in cells from aged animals. When LVA currents were studied without activation of high voltage activated currents, the current density (pA/pF) was significantly (P < 0.05) increased at negative potentials in aged neurons (young: 4.92 +/- 0.35 pA/pF; Aged: 5.92 +/- 0.45 pA/pF, at a prepulse potential of -110 mV). No change in voltage-dependent activation or inactivation was seen. The time course of recovery from inactivation also was unchanged. 4. Kinetic parameters of LVA currents were compared in both age groups. No age-related difference in time-dependent activation or inactivation was observed. A single distribution of decay time constants of LVA currents was present in both age groups. 5. These results show that MS/nDB cells maintain robust LVA currents and have increased current densities in very old rats. An increased LVA current in the aged neurons suggests that their ability to fire rhythmically or in bursts is retained or enhanced and that the resulting increase in intracellular Ca2+ may contribute to an altered Ca2+ homeostasis.

The Cl- channel TMEM16A controls the generation of cochlear Ca2+ waves and promotes the refinement of auditory brainstem networks

2021 ◽  
Author(s):  
Alena Maul ◽  
Saša Jovanovic ◽  
Antje-Kathrin Huebner ◽  
Nicola Strenzke ◽  
Tobias Moser ◽  
...  
Keyword(s):  
Hair Cells ◽  
Action Potentials ◽  
Auditory Pathway ◽  
Auditory Brainstem ◽  
Supporting Cells ◽  
Cl Channel ◽  
Medial Nucleus ◽  
Conditional Deletion ◽  
Sensory Activity ◽  
Trapezoid Body

Before hearing onset (postnatal day 12 in mice), inner hair cells (IHC) spontaneously fire action potentials thereby driving pre-sensory activity in the ascending auditory pathway. The rate of IHC action potential bursts is modulated by inner supporting cells (ISC) of Kölliker's organ through the activity of the Ca2+ activated Cl- channel TMEM16A. Here we show that conditional deletion of Tmem16a in mice disrupts the generation of Ca2+ waves within Köllike's organ, reduces the burst firing activity and the frequency-selectivity of auditory brainstem neurons in the medial nucleus of the trapezoid body (MNTB), and also impairs the refinement of MNTB projections to the lateral superior olive (LSO). These results reveal the importance of the activity of Köllike's organ for the refinement of central auditory connectivity. In addition, our study suggests a mechanism for the generation of Ca2+ waves, which may also apply to other tissues expressing TMEM16A.

The Brain Stem Evoked Response and Medial Nucleus of the Trapezoid Body

1994 ◽  
Vol 110 (1) ◽  
pp. 84-92 ◽  
Author(s):  
Chiyeko Tsuchitani
Keyword(s):  
Brain Stem ◽  
Action Potentials ◽  
Stimulus Onset ◽  
Evoked Response ◽  
Superior Olivary Complex ◽  
Lateral Superior Olive ◽  
Medial Nucleus ◽  
Brain Stem Evoked Response ◽  
The Brain ◽  
Trapezoid Body

Single-unit responses of cat superior olivary complex neurons to acoustic stimuli were examined to determine whether the units' action potentials were sufficiently synchronized to contribute to the brain stem evoked response. The medial nucleus of the trapezoid body and lateral superior olive are two major nuclei within the cat superior olivary complex. The first-spike discharge latencies of medial nucleus of the trapezoid body and lateral superior olivary neurons to monaural presentations of tone burst stimuli were measured as a function of stimulus level. Evidence is provided to support the hypotheses that in cat the medial nucleus of the trapezoid body may contribute directly to the monaural brain stem evoked response by producing action potentials synchronized to stimulus onset and may also contribute indirectly to the brain stem evoked response binaural difference wave bc by inhibiting the lateral superior olive unit excitatory responses synchronized to stimulus onset.

scholarly journals Minireview: Aldosterone Biosynthesis: Electrically Gated for Our Protection

Endocrinology ◽  
2012 ◽  
Vol 153 (8) ◽  
pp. 3579-3586 ◽  
Author(s):  
Nick A. Guagliardo ◽  
Junlan Yao ◽  
Changlong Hu ◽  
Paula Q. Barrett
Keyword(s):  
Time Course ◽  
Low Voltage ◽  
Salt Water ◽  
Zona Glomerulosa ◽  
Membrane Voltage ◽  
Disease States ◽  
Voltage Dependent ◽  
Aldosterone Production ◽  
Ca2 Channels

Aldosterone produced by adrenal zona glomerulosa (ZG) cells plays an important role in maintaining salt/water balance and, hence, blood pressure homeostasis. However, when dysregulated, aldosterone advances renal and cardiovascular disease states. Multiple steps in the steroidogenic pathway require Ca2+, and the sustained production of aldosterone depends on maintained Ca2+ entry into the ZG cell. Nevertheless, the recorded membrane potential of isolated ZG cells is extremely hyperpolarized, allowing the opening of only a small fraction of low-voltage-activated Ca2+ channels of the Cav3.x family, the major Ca2+ conductance on the ZG cell membrane. As a consequence, to activate sufficient Ca2+ channels to sustain the production of aldosterone, aldosterone secretagogs would be required to affect large decreases in membrane voltage, a requirement that is inconsistent with the exquisite sensitivity of aldosterone production in vivo to small changes (0.1 mm) in extracellular K+. In this review, we evaluate the contribution of membrane voltage and voltage-dependent Ca2+ channels to the control of aldosterone production and consider data highlighting the electrical excitability of the ZG cell. This intrinsic capacity of ZG cells to behave as electrical oscillators provides a platform from which to generate a recurring Ca2+ signal that is compatible with the lengthy time course of steroidogenesis and provides an alternative model for the physiological regulation of aldosterone production that permits both amplitude and temporal modulation of the Ca2+ signal.

scholarly journals Background Synaptic Conductance and Precision of EPSP-Spike Coupling at Pyramidal Cells

2005 ◽  
Vol 93 (6) ◽  
pp. 3248-3256 ◽  
Author(s):  
Veronika Zsiros ◽  
Shaul Hestrin
Keyword(s):  
Time Course ◽  
Pyramidal Cells ◽  
Spike Timing ◽  
Synaptic Activity ◽  
Synaptic Conductance ◽  
Temporal Precision ◽  
Voltage Dependent ◽  
Cortical Slices

The temporal precision of converting excitatory postsynaptic potentials (EPSPs) into spikes at pyramidal cells is critical for the coding of information in the cortex. Several in vitro studies have shown that voltage-dependent conductances in pyramidal cells can prolong the EPSP time course resulting in an imprecise EPSP-spike coupling. We have used dynamic-clamp techniques to mimic the in vivo background synaptic conductance in cortical slices and investigated how the ongoing synaptic activity may affect the EPSP time course near threshold and the EPSP spike coupling. We report here that background synaptic conductance dramatically diminished the depolarization related prolongation of the EPSPs in pyramidal cells and improved the precision of spike timing. Furthermore, we found that background synaptic conductance can affect the interaction among action potentials in a spike train. Thus the level of ongoing synaptic activity in the cortex may regulate the capacity of pyramidal cells to process temporal information.

Differences in presynaptic action of 4-aminopyridine and tetraethylammonium at frog neuromuscular junction

1987 ◽  
Vol 65 (5) ◽  
pp. 747-752 ◽  
Author(s):  
M. I. Glavinović
Keyword(s):  
Neuromuscular Junction ◽  
Transmitter Release ◽  
Action Potentials ◽  
Time Course ◽  
Potassium Conductance ◽  
Frog Neuromuscular Junction ◽  
Quantal Content ◽  
Low Concentrations ◽  
Voltage Dependent ◽  
Intracellular Ca

4-Aminopyridine markedly potentiates transmitter release at the frog cutaneous pectoris neuromuscular junction by increasing the quantal content even when applied at low concentrations (5–20 μM). This enhancement of transmitter release is associated with greater minimum synaptic latency, but the dispersion of the synaptic latencies does not appear much affected. This is in contrast with the action of tetraethylammonium (0.2–0.5 mM) in which case similar enhancement of transmitter release results not only in larger minimum synaptic latency but also in greater dispersion of the synaptic latencies. The time course of transmitter release associated with enhanced transmitter output is hence much more prolonged in the presence of tetraethylammonium than 4-aminopyridine, at least for low concentrations of 4-aminopyridine (5–20 μM). This indicates that their presynaptic actions differ significantly. This conclusion is further strengthened by the finding that unlike tetraethylammonium, 4-aminopyridine induces bursts of release, presumably by producing multiple action potentials in the nerve terminal. Tetraethylammonium probably acts by blocking the delayed potassium conductance, but the blockade of Ca2+-activated K+ conductance cannot be excluded. 4-Aminopyridine, however, probably blocks the fast inactivating (IA) K+ current, but it also may be acting directly on the voltage-dependent Ca2+ conductance or on the intracellular Ca2+ buffering.

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