Ca2+-activated ion currents triggered by ryanodine receptor-mediated Ca2+release control firing of inhibitory neurons in the prepositus hypoglossi nucleus

2013 ◽  
Vol 109 (2) ◽  
pp. 389-404 ◽  
Author(s):  
Yasuhiko Saito ◽  
Yuchio Yanagawa
Keyword(s):  
Ryanodine Receptors ◽  
Smooth Muscles ◽  
Firing Frequency ◽  
Neuronal Firing ◽  
Inhibitory Neurons ◽  
Sk Channels ◽  
Spontaneous Firing ◽  
Central Neurons ◽  
Outward Currents ◽  
Prepositus Hypoglossi

Spontaneous miniature outward currents (SMOCs) are known to exist in smooth muscles and peripheral neurons, and evidence for the presence of SMOCs in central neurons has been accumulating. SMOCs in central neurons are induced through Ca2+-activated K+(KCa) channels, which are activated through Ca2+-induced Ca2+release from the endoplasmic reticulum via ryanodine receptors (RyRs). Previously, we found that some neurons in the prepositus hypoglossi nucleus (PHN) showed spontaneous outward currents (SOCs). In the present study, we used whole cell recordings in slice preparations of the rat brain stem to investigate the following: 1) the ionic mechanisms of SOCs, 2) the types of neurons exhibiting frequent SOCs, and 3) the effect of Ca2+-activated conductance on neuronal firing. Pharmacological analyses revealed that SOCs were induced via the activation of small-conductance-type KCa(SK) channels and RyRs, indicating that SOCs correspond to SMOCs. An analysis of the voltage responses to current pulses of the fluorescence-expressing inhibitory neurons of transgenic rats revealed that inhibitory neurons frequently exhibited SOCs. Abolition of SOCs via blockade of SK channels enhanced the frequency of spontaneous firing of inhibitory PHN neurons. However, abolition of SOCs via blockade of RyRs reduced the firing frequency and hyperpolarized the membrane potential. Similar reductions in firing frequency and hyperpolarization were also observed when Ca2+-activated nonselective cation (CAN) channels were blocked. These results suggest that, in inhibitory neurons in the PHN, Ca2+release via RyRs activates SK and CAN channels, and these channels regulate spontaneous firing in a complementary manner.

scholarly journals Intracellular calcium events activated by ATP in murine colonic myocytes

2000 ◽  
Vol 279 (1) ◽  
pp. C126-C135 ◽  
Author(s):  
Orline Bayguinov ◽  
Brian Hagen ◽  
Adrian D. Bonev ◽  
Mark T. Nelson ◽  
Kenton M. Sanders
Keyword(s):  
Ryanodine Receptors ◽  
Smooth Muscles ◽  
Sk Channels ◽  
Inhibitory Neurotransmitter ◽  
Outward Currents ◽  
Ionic Conductances ◽  
Visceral Muscles ◽  
Murine Colon ◽  
Spontaneous Transient Outward Currents ◽  
Purinergic Stimulation

ATP is a candidate enteric inhibitory neurotransmitter in visceral smooth muscles. ATP hyperpolarizes visceral muscles via activation of small-conductance, Ca2+-activated K+ (SK) channels. Coupling between ATP stimulation and SK channels may be mediated by localized Ca2+ release. Isolated myocytes of the murine colon produced spontaneous, localized Ca2+ release events. These events corresponded to spontaneous transient outward currents (STOCs) consisting of charybdotoxin (ChTX)-sensitive and -insensitive events. ChTX-insensitive STOCs were inhibited by apamin. Localized Ca2+ transients were not blocked by ryanodine, but these events were reduced in magnitude and frequency by xestospongin C (Xe-C), a blocker of inositol 1,4,5-trisphosphate receptors. Thus we have termed the localized Ca2+ events in colonic myocytes “Ca2+ puffs.” The P2Y receptor agonist 2-methylthio-ATP (2-MeS-ATP) increased the intensity and frequency of Ca2+ puffs. 2-MeS-ATP also increased STOCs in association with the increase in Ca2+ puffs. Pyridoxal-phospate-6-azophenyl-2′,4′-disculfonic acid tetrasodium, a P2 receptor inhibitor, blocked responses to 2-MeS-ATP. Spontaneous Ca2+ transients and the effects of 2-MeS-ATP on Ca2+ puffs and STOCs were blocked by U-73122, an inhibitor of phospholipase C. Xe-C and ryanodine also blocked responses to 2-MeS-ATP, suggesting that, in addition to release from IP3receptor-operated stores, ryanodine receptors may be recruited during agonist stimulation to amplify release of Ca2+. These data suggest that localized Ca2+ release modulates Ca2+-dependent ionic conductances in the plasma membrane. Localized Ca2+ release may contribute to the electrical responses resulting from purinergic stimulation.

Spontaneous Ryanodine-Receptor-Dependent Ca2+-Activated K+ Currents and Hyperpolarizations in Rat Medial Preoptic Neurons

2010 ◽  
Vol 103 (5) ◽  
pp. 2900-2911 ◽  
Author(s):  
Göran Klement ◽  
Michael Druzin ◽  
David Haage ◽  
Evgenya Malinina ◽  
Peter Århem ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Ryanodine Receptors ◽  
Underlying Mechanism ◽  
Sk Channels ◽  
Patch Clamp Technique ◽  
Channel Activation ◽  
Impulse Generation ◽  
Outward Currents ◽  
Main Charge ◽  
Perforated Patch Clamp

The aim of the present study was to clarify the identity of slow spontaneous currents, the underlying mechanism and possible role for impulse generation in neurons of the rat medial preoptic nucleus (MPN). Acutely dissociated neurons were studied with the perforated patch-clamp technique. Spontaneous outward currents, at a frequency of ∼0.5 Hz and with a decay time constant of ∼200 ms, were frequently detected in neurons when voltage-clamped between approximately −70 and −30 mV. The dependence on extracellular K+ concentration was consistent with K+ as the main charge carrier. We concluded that the main characteristics were similar to those of spontaneous miniature outward currents (SMOCs), previously reported mainly for muscle fibers and peripheral nerve. From the dependence on voltage and from a pharmacological analysis, we concluded that the currents were carried through small-conductance Ca2+-activated (SK) channels, of the SK3 subtype. From experiments with ryanodine, xestospongin C, and caffeine, we concluded that the spontaneous currents were triggered by Ca2+ release from intracellular stores via ryanodine receptor channels. An apparent voltage dependence was explained by masking of the spontaneous currents as a consequence of steady SK-channel activation at membrane potentials > −30 mV. Under current-clamp conditions, corresponding transient hyperpolarizations occasionally exceeded 10 mV in amplitude and reduced the frequency of spontaneous impulses. In conclusion, MPN neurons display spontaneous hyperpolarizations triggered by Ca2+ release via ryanodine receptors and SK3-channel activation. Thus such events may affect impulse firing of MPN neurons.

Effects of Nucleus Prepositus Hypoglossi Lesions on Visual Climbing Fiber Activity in the Rabbit Flocculus

2000 ◽  
Vol 84 (5) ◽  
pp. 2552-2563 ◽  
Author(s):  
M. P. Arts ◽  
C. I. De Zeeuw ◽  
J. Lips ◽  
E. Rosbak ◽  
J. I. Simpson
Keyword(s):  
Constant Velocity ◽  
Inferior Olive ◽  
Vertical Axis ◽  
Firing Frequency ◽  
Optokinetic Stimulation ◽  
Spontaneous Firing ◽  
Complex Spike ◽  
Prepositus Hypoglossi ◽  
Complex Spikes ◽  
Spike Firing

The caudal dorsal cap (dc) of the inferior olive is involved in the control of horizontal compensatory eye movements. It provides those climbing fibers to the vestibulocerebellum that modulate optimally to optokinetic stimulation about the vertical axis. This modulation is mediated at least in part via an excitatory input to the caudal dc from the pretectal nucleus of the optic tract and the dorsal terminal nucleus of the accessory optic system. In addition, the caudal dc receives a substantial GABAergic input from the nucleus prepositus hypoglossi (NPH). To investigate the possible contribution of this bilateral inhibitory projection to the visual responsiveness of caudal dc neurons, we recorded the climbing fiber activity (i.e., complex spikes) of vertical axis Purkinje cells in the flocculus of anesthetized rabbits before and after ablative lesions of the NPH. When the NPH ipsilateral to the recorded flocculus was lesioned, the spontaneous complex spike firing frequency did not change significantly; but when both NPHs were lesioned, the spontaneous complex spike firing frequency increased significantly. When only the contralateral NPH was lesioned, the spontaneous complex spike firing frequency decreased significantly. Neither unilateral nor bilateral lesions had a significant influence on the depth of complex spike modulation during constant velocity optokinetic stimulation or on the transient continuation of complex spike modulation that occurred when the constant velocity optokinetic stimulation stopped. The effects of the lesions on the spontaneous complex spike firing frequency could not be explained when only the projections from the NPH to the inferior olive were considered. Therefore we investigated at the electron microscopic level the nature of the commissural connection between the two NPHs. The terminals of this projection were found to be predominantly GABAergic and to terminate in part on GABAergic neurons. When this inhibitory commissural connection is taken into consideration, then the effects of NPH lesions on the spontaneous firing frequency of floccular complex spikes are qualitatively explicable in terms of relative weighting of the commissural and caudal dc projections of the NPH. In summary, we conclude that in the anesthetized rabbit the inhibitory projection of the NPH to the caudal dc influences the spontaneous firing frequency of floccular complex spikes but not their modulation by optokinetic stimulation.

scholarly journals Kv3 channels contribute to the excitability of sub-populations of spinal cord neurons in lamina VII

2021 ◽  
Author(s):  
Pierce Mullen ◽  
Nadia Pilati ◽  
Charles H Large ◽  
Jim Deuchars ◽  
Susan A Deuchars
Keyword(s):  
Spinal Cord ◽  
Firing Frequency ◽  
Neuronal Firing ◽  
Recurrent Inhibition ◽  
Inhibitory Neurons ◽  
Spinal Cord Neurons ◽  
Lumbosacral Spinal Cord ◽  
Whole Cell Patch Clamp ◽  
Neuronal Types ◽  
Fast Firing

Autonomic parasympathetic preganglionic neurons (PGN) drive contraction of the bladder during micturition but remain quiescent during bladder filling. This quiescence is postulated to be due to recurrent inhibition of PGN by fast-firing adjoining interneurons. Here, we defined four distinct neuronal types within lamina VII of the lumbosacral spinal cord, where PGN are situated, by combining whole cell patch clamp recordings with k-means clustering of a range of electrophysiological parameters. Additional morphological analysis separated these neuronal classes into parasympathetic preganglionic populations (PGN) and a fast firing interneuronal population. Kv3 channels are voltage-gated potassium channels (Kv) that allow fast and precise firing of neurons. We found that blockade of Kv3 channels by tetraethylammonium (TEA) reduced neuronal firing frequency and isolated high-voltage-activated Kv currents in the fast-firing population but had no effect in PGN populations. Furthermore, Kv3 blockade potentiated the local and descending inhibitory inputs to PGN indicating that Kv3-expressing inhibitory neurons are synaptically connected to PGN. Taken together, our data reveal that Kv3 channels are crucial for fast and regulated neuronal output of a defined population that may be involved in intrinsic spinal bladder circuits that underpin recurrent inhibition of PGN.

Single-unit analysis of different hippocampal cell types during classical conditioning of rabbit nictitating membrane response

1983 ◽  
Vol 50 (5) ◽  
pp. 1197-1219 ◽  
Author(s):  
T. W. Berger ◽  
P. C. Rinaldi ◽  
D. J. Weisz ◽  
R. F. Thompson
Keyword(s):  
Classical Conditioning ◽  
Pyramidal Cell ◽  
Action Potentials ◽  
Pyramidal Cells ◽  
Cell Types ◽  
Firing Frequency ◽  
Spontaneous Firing ◽  
Nictitating Membrane ◽  
Nictitating Membrane Response ◽  
Firing Characteristics

Extracellular single-unit recordings from neurons in the CA1 and CA3 regions of the dorsal hippocampus were monitored during classical conditioning of the rabbit nictitating membrane response. Neurons were classified as different cell types using response to fornix stimulation (i.e., antidromic or orthodromic activation) and spontaneous firing characteristics as criteria. Results showed that hippocampal pyramidal neurons exhibit learning-related neural plasticity that develops gradually over the course of classical conditioning. The learning-dependent pyramidal cell response is characterized by an increase in frequency of firing within conditioning trials and a within-trial pattern of discharge that correlates strongly with amplitude-time course of the behavioral response. In contrast, pyramidal cell activity recorded from control animals given unpaired presentations of the conditioned and unconditioned stimulus (CS and UCS) does not show enhanced discharge rates with repeated stimulation. Previous studies of hippocampal cellular electrophysiology have described what has been termed a theta-cell (19-21, 45), the activity of which correlates with slow-wave theta rhythm generated in the hippocampus. Neurons classified as theta-cells in the present study exhibit responses during conditioning that are distinctly different than pyramidal cells. theta-Cells respond during paired conditioning trials with a rhythmic bursting; the between-burst interval occurs at or near 8 Hz. In addition, two different types of theta-cells were distinguishable. One type of theta-cell increases firing frequency above pretrial levels while displaying the theta bursting pattern. The other type decreases firing frequency below pretrial rates while showing a theta-locked discharge. In addition to pyramidal and theta-neurons, several other cell types recorded in or near the pyramidal cell layer could be distinguished. One cell type was distinctive in that it could be activated with a short, invariant latency following fornix stimulation, but spontaneous action potentials of such neurons could not be collided with fornix shock-induced action potentials. These neurons exhibit a different profile of spontaneous firing characteristics than those of antidromically identified pyramidal cells. Nevertheless, neurons in this noncollidable category display the same learning-dependent response as pyramidal cells. It is suggested that the noncollidable neurons represent a subpopulation of pyramidal cells that do not project an axon via the fornix but project, instead, to other limbic cortical regions.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Coupling of SK channels, L-type Ca2+ channels, and ryanodine receptors in cardiomyocytes

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Xiao-Dong Zhang ◽  
Zana A. Coulibaly ◽  
Wei Chun Chen ◽  
Hannah A. Ledford ◽  
Jeong Han Lee ◽  
...  
Keyword(s):  
Ryanodine Receptors ◽  
Sk Channels ◽  
Ca2 Channels

scholarly journals Firing responses mediated via distinct nicotinic acetylcholine receptor subtypes in rat prepositus hypoglossi nuclei neurons

2018 ◽  
Vol 120 (4) ◽  
pp. 1525-1533
Author(s):  
Yue Zhang ◽  
Yuchio Yanagawa ◽  
Yasuhiko Saito
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Firing Frequency ◽  
Membrane Properties ◽  
Receptor Subtypes ◽  
Nicotinic Acetylcholine ◽  
Firing Patterns ◽  
Prepositus Hypoglossi ◽  
Specific Antagonist ◽  
The Relationship

We previously reported that cholinergic current responses mediated via nicotinic acetylcholine (ACh) receptors (nAChRs) in the prepositus hypoglossi nucleus (PHN), which participates in gaze control, can be classified into distinct types based on different kinetics and are mainly composed of α7- and/or non-α7-subtypes: fast (F)-, slow (S)-, and fast and slow (FS)-type currents. In this study, to clarify how each current type is related to neuronal activities, we investigated the relationship between the current types and the membrane properties and the firing responses that were induced by each current type. The proportion of the current types differed in neurons that exhibited different afterhyperpolarization (AHP) profiles and firing patterns, suggesting that PHN neurons show a preference for specific current types dependent on the membrane properties. In response to ACh, F-type neurons showed either one action potential (AP) or multiple APs with a short firing duration, and S-type neurons showed multiple APs with a long firing duration. The firing frequency of F-type neurons was significantly higher than that of S-type and FS-type neurons. An α7-subtype-specific antagonist abolished the firing responses of F-type neurons and reduced the responses of FS-type neurons but had little effect on the responses of S-type neurons, which were reduced by a non-α7-subtype-specific antagonist. These results suggest that the different properties of the current types and the distinct expression of the nAChR subtypes in PHN neurons with different membrane properties produce unique firing responses via the activation of nAChRs. NEW & NOTEWORTHY Prepositus hypoglossi nucleus (PHN) neurons show distinct nicotinic acetylcholine receptor (nAChR)-mediated current responses. The proportion of the current types differed in the neurons that exhibited different afterhyperpolarization profiles and firing patterns. The nAChR-mediated currents with different kinetics induced firing responses of the neurons that were distinct in the firing frequency and duration. These results suggest that the different properties of the current types in PHN neurons with different membrane properties produce unique firing responses via the activation of nAChRs.

scholarly journals Coupling of L-Type Ca2+ Channels to KV7/KCNQ Channels Creates a Novel, Activity-Dependent, Homeostatic Intrinsic Plasticity

2008 ◽  
Vol 100 (4) ◽  
pp. 1897-1908 ◽  
Author(s):  
Wendy W. Wu ◽  
C. Savio Chan ◽  
D. James Surmeier ◽  
John F. Disterhoft
Keyword(s):  
Pyramidal Neurons ◽  
Firing Frequency ◽  
Fine Tuning ◽  
Membrane Excitability ◽  
Kcnq Channels ◽  
Central Neurons ◽  
Subsequent Activation ◽  
Intrinsic Plasticity ◽  
Dependent Modification ◽  
Activity Dependent

Experience-dependent modification in the electrical properties of central neurons is a form of intrinsic plasticity that occurs during development and has been observed following behavioral learning. We report a novel form of intrinsic plasticity in hippocampal CA1 pyramidal neurons mediated by the KV7/KCNQ and CaV1/L-type Ca2+ channels. Enhancing Ca2+ influx with a conditioning spike train (30 Hz, 3 s) potentiated the KV7/KCNQ channel function and led to a long-lasting, activity-dependent increase in spike frequency adaptation—a gradual reduction in the firing frequency in response to sustained excitation. These effects were abolished by specific blockers for CaV1/L-type Ca2+ channels, KV7/KCNQ channels, and protein kinase A (PKA). Considering the widespread expression of these two channel types, the influence of Ca2+ influx and subsequent activation of PKA on KV7/KCNQ channels may represent a generalized principle in fine tuning the output of central neurons that promotes stability in firing—an example of homeostatic regulation of intrinsic membrane excitability.

Electrophysiological Differences Between Neurogliaform Cells From Monkey and Rat Prefrontal Cortex

2007 ◽  
Vol 97 (2) ◽  
pp. 1030-1039 ◽  
Author(s):  
N. V. Povysheva ◽  
A. V. Zaitsev ◽  
S. Kröner ◽  
O. A. Krimer ◽  
D. C. Rotaru ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Input Resistance ◽  
Firing Frequency ◽  
Morphological Features ◽  
Inhibitory Neurons ◽  
Physiological Properties ◽  
Cortical Circuit ◽  
Current Steps ◽  
Constituent Elements ◽  
Whole Cell Recordings

Current dogma holds that a canonical cortical circuit is formed by cellular elements that are basically identical across species. However, detailed and direct comparisons between species of specific elements of this circuit are limited in number. In this study, we compared the morphological and physiological properties of neurogliaform (NGF) inhibitory neurons in the prefrontal cortex (PFC) of macaque monkeys and rats. In both species, NGF cells were readily identified based on their distinctive morphological features. Indeed, monkey NGF cells had only a few morphological features that differed from rat, including a larger soma, a greater number of dendrites, and a more compact axonal field. In contrast, whole cell recordings of the responses to injected current steps revealed important differences between monkey and rat NGF cells. Monkey NGF cells consistently generated a short-latency first spike riding on an initial depolarizing hump, whereas in rat NGF cells, the first spike appeared after a substantial delay riding on a depolarizing ramp not seen in monkey NGF cells. Thus although rat NGF cells are traditionally classified as late-spiking cells, monkey NGF cells did not meet this physiological criterion. In addition, NGF cells in monkey appeared to be more excitable than those in rat because they displayed a higher input resistance, a lower spike threshold, and a higher firing frequency. Finally, NGF cells in monkey showed a more prominent spike-frequency adaptation as compared with rat. Our findings indicate that the canonical cortical circuit differs in at least some aspects of its constituent elements across species.

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