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Spontaneous Firing (spontaneous + firing)
Selected AbstractsSpontaneous Pulmonary Vein Firing in Man: Relationship to Tachycardia-Pause Early Afterdepolarizations and Triggered Arrhythmia in Canine Pulmonary Veins In VitroJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 10 2007EUGENE PATTERSON Ph.D. Introduction: Rapid firing originating within pulmonary veins (PVs) initiates atrial fibrillation (AF). The following studies were performed to evaluate spontaneous PV firing in patients with AF to distinguish focal versus reentrant mechanisms. Methods: Intracardiac recordings were obtained in 18 patients demonstrating paroxysmal AF. Microelectrode (ME) recordings were obtained from superfused canine PV sleeves (N = 48). Results: Spontaneous PV firing (566 ± 16 bpm; 127 ± 6 ms cycle length) giving rise to AF (52 episodes) was observed. Tachycardia-pause initiation was present in 132 of 200 episodes of rapid PV firing and 34 of 52 AF episodes. The pause cycle length preceding PV firing was 1,039 ± 86 ms following tachycardia (420 ± 40 ms cycle length). The remaining episodes were initiated following a 702 ± 32 ms pause during sinus rhythm (588 ± 63 ms). Spontaneous firing recorded with a multipolar mapping catheter did not detect electrical activity bridging the diastolic interval between the initial ectopic and preceding post-pause sinus beat. Tachycardia-pause initiated PV firing (138 ± 7 ms coupling interval) in patients correlated with tachycardia-pause enhanced isometric force, early afterdepolarization (EAD) amplitude, and triggered firing within canine PVs. Rapid firing (1,172 ± 134 bpm; 51 ± 8 ms cycle length) following an abbreviated coupling interval (69 ± 12 ms) was initiated in 13 of 18 canine PVs following tachycardia-pause pacing during norepinephrine + acetylcholine superfusion. Stimulation selectively activating local autonomic nerve terminals facilitated tachycardia-pause triggered firing in canine PVs (5 of 15 vs 0 of 15; P < 0.05). Conclusions: The studies demonstrate (1) tachycardia-pause initiation of rapid, short-coupled PV firing in AF patients and (2) tachycardia-pause facilitation of isometric force, EAD formation, and autonomic-dependent triggered firing within canine PVs, suggestive of a common arrhythmia mechanism. [source] Neonatal nociceptive somatic stimulation differentially modifies the activity of spinal neurons in rats and results in altered somatic and visceral sensationTHE JOURNAL OF PHYSIOLOGY, Issue 3 2006Adrian Miranda The role of intramuscular, low pH saline injections during the neonatal period in the development and maintenance of visceral hyperalgesia has not been systematically studied. We aimed to investigate alterations in visceral sensation and neural circuitry that result from noxious stimuli in early life. Neonatal male Sprague,Dawley rats received sterile saline injections of pH 4.0 or 7.4 in the gastrocnemius muscle starting at postnatal day 8. Injections were given unilaterally every other day for 12 days ending on postnatal day 20. A third group received needle prick only on the same shedule as the second group, while a fourth group was left naïve. At 2 months of age, rats underwent assessment of cutaneous and deep somatic sensitivity using von Frey filaments and gastrocnemius muscle pinch, respectively. A visceromotor response (VMR) to graded colorectal distension (CRD; 10,80 mmHg for 30 s with 180 s interstimulus intervals) was recorded. Extracellular single-unit recordings from the thoracolumbar spinal neurons (T13,L1) were performed in adult pH 4.0 injected and naïve controls. There was no difference in the threshold for response to mechanical stimulation of the paw in rats injected with pH 4.0 saline compared to all other groups. Conversely, rats treated with pH 4.0 saline showed a significant bilateral reduction in withdrawal threshold to muscle pinch as adults (P < 0.05). At colorectal distensions , 20 mmHg, an increase in the VMR was observed in the pH 4.0 injected group compared to all other groups (P < 0.05). Spinal neurons were classified as short latency abrupt (SL-A) or short latency sustained (SL-S). Spontaneous firing of SL-S (20.6 ± 2.2 impulses s,1), but not SL-A neurons (5.3 ± 0.9 impulses s,1) in the pH 4.0 treated rats was significantly higher than in control rats (SL-S, 2.6 ± 0.8 impulses s,1; SL-A, 3.1 ± 0.7 impulses s,1). The response of SL-S neurons to CRD in the pH 4.0 group was significantly higher at distension pressures , 20 mmHg. Nociceptive somatic stimulation in neonatal rats results in chronic deep somatic and visceral hyperalgesia in adulthood. Colorectal distension-sensitive SL-S neurons are primarily sensitized to neonatal somatic stimulation. [source] Tonically active neurons in the primate striatum and their role in the processing of information about motivationally relevant eventsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2002Paul ApicellaArticle first published online: 11 DEC 200 Abstract Analysis of recordings of single neuronal activity in the striatum of monkeys engaged in behavioural tasks has shown that tonically active neurons (TANs) can be distinguished by their distinct spontaneous firing and functional properties. As TANs are assumed to be cholinergic interneurons, the study of their physiological characteristics allows us to gain an insight into the role of a particular type of local-circuit neuron in the processing of information at the striatal level. In monkeys performing various behavioural tasks, the change in the activity of TANs, unlike the diversity of task-related activations exhibited by the phasically active population of striatal neurons, involves a transient depression of the tonic firing related to environmental events of motivational significance. Such events include primary rewards and stimuli that have acquired a reward value during associative learning. These neurons also respond to an aversive air puff, indicating that their responsiveness is not restricted to appetitive conditions. Another striking feature of the TANs is that their responses can be modulated by predictions about stimulus timing. Temporal variations in event occurrence have been found to favour the responses of TANs, whereas the responses are diminished or abolished in the presence of external cues that predict the time at which events will occur. These data suggest that the TANs respond as do detectors of motivationally relevant events, but they also demonstrate that these neurons are influenced by predictive information based on past experience with a given temporal context. TANs represent a unique subset of striatal neurons that might serve a modulatory function, monitoring for temporal relationships between environmental events. [source] Dependence of Hyperpolarisation-Activated Cyclic Nucleotide-Gated Channel Activity on Basal Cyclic Adenosine Monophosphate Production in Spontaneously Firing GH3 CellsJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2006K. Kretschmannova Abstract The hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels play a distinct role in the control of membrane excitability in spontaneously active cardiac and neuronal cells. Here, we studied the expression and role of HCN channels in pacemaking activity, Ca2+ signalling, and prolactin secretion in GH3 immortalised pituitary cells. Reverse transcriptase-polymerase chain reaction analysis revealed the presence of mRNA transcripts for HCN2, HCN3 and HCN4 subunits in these cells. A hyperpolarisation of the membrane potential below ,,60 mV elicited a slowly activating voltage-dependent inward current (Ih) in the majority of tested cells, with a half-maximal activation voltage of ,89.9 ± 4.2 mV and with a time constant of 1.4 ± 0.2 s at ,120 mV. The bath application of 1 mM Cs+, a commonly used inorganic blocker of Ih, and 100 µM ZD7288, a specific organic blocker of Ih, inhibited Ih by 90 ± 4.1% and 84.3 ± 1.8%, respectively. Receptor- and nonreceptor-mediated activation of adenylyl and soluble guanylyl cyclase and the addition of a membrane permeable cyclic adenosine monophosphate (cAMP) analogue, 8-Br-cAMP, did not affect Ih. Inhibition of basal adenylyl cyclase activity, but not basal soluble guanylyl cyclase activity, led to a reduction in the peak amplitude and a leftward shift in the activation curve of Ih by 23.7 mV. The inhibition of the current was reversed by stimulation of adenylyl cyclase with forskolin and by the addition of 8-Br-cAMP, but not 8-Br-cGMP. Application of Cs+ had no significant effect on the resting membrane potential or electrical activity, whereas ZD7288 exhibited complex and Ih -independent effects on spontaneous electrical activity, Ca2+ signalling, and prolactin release. These results indicate that HCN channels in GH3 cells are under tonic activation by basal level of cAMP and are not critical for spontaneous firing of action potentials. [source] Accumulation of cytoplasmic calcium, but not apamin-sensitive afterhyperpolarization current, during high frequency firing in rat subthalamic nucleus cellsTHE JOURNAL OF PHYSIOLOGY, Issue 3 2008Mark Teagarden The autonomous firing pattern of neurons in the rat subthalamic nucleus (STN) is shaped by action potential afterhyperpolarization currents. One of these is an apamin-sensitive calcium-dependent potassium current (SK). The duration of SK current is usually considered to be limited by the clearance of calcium from the vicinity of the channel. When the cell is driven to fire faster, calcium is expected to accumulate, and this is expected to result in accumulation of calcium-dependent AHP current. We measured the time course of calcium transients in the soma and proximal dendrites of STN neurons during spontaneous firing and their accumulation during driven firing. We compared these to the time course and accumulation of AHP currents using whole-cell and perforated patch recordings. During spontaneous firing, a rise in free cytoplasmic calcium was seen after each action potential, and decayed with a time constant of about 200 ms in the soma, and 80 ms in the dendrites. At rates higher than 10 Hz, calcium transients accumulated as predicted. In addition, there was a slow calcium transient not predicted by summation of action potentials that became more pronounced at high firing frequency. Spike AHP currents were measured in voltage clamp as tail currents after 2 ms voltage pulses that triggered action currents. Apamin-sensitive AHP (SK) current was measured by subtraction of tail currents obtained before and after treatment with apamin. SK current peaked between 10 and 15 ms after an action potential, had a decay time constant of about 30 ms, and showed no accumulation. At frequencies between 5 and 200 spikes s,1, the maximal SK current remained the same as that evoked by a single action potential. AHP current did not have time to decay between action potentials, so at frequencies above 50 spikes s,1 the apamin-sensitive current was effectively constant. These results are inconsistent with the view that the decay of SK current is governed by calcium dynamics. They suggest that the calcium is present at the SK channel for a very short time after each action potential, and the current decays at a rate set by the deactivation kinetics of the SK channel. At high rates, repetitive firing was governed by a fast apamin-insensitive AHP current that did not accumulate, but rather showed depression with increases in activation frequency. A slowly accumulating AHP current, also insensitive to apamin, was extremely small at low rates but became significant with higher firing rates. [source] Intrinsic properties and mechanisms of spontaneous firing in mouse cerebellar unipolar brush cellsTHE JOURNAL OF PHYSIOLOGY, Issue 2 2007Marco J. Russo Neuronal firing patterns are determined by the cell's intrinsic electrical and morphological properties and are regulated by synaptic interactions. While the properties of cerebellar neurons have generally been studied in much detail, little is known about the unipolar brush cells (UBCs), a type of glutamatergic interneuron that is enriched in the granular layer of the mammalian vestibulocerebellum and participates in the representation of head orientation in space. Here we show that UBCs can be distinguished from adjacent granule cells on the basis of differences in membrane capacitance, input resistance and response to hyperpolarizing current injection. We also show that UBCs are intrinsically firing neurons. Using action potential clamp experiments and whole-cell recordings we demonstrate that two currents contribute to this property: a persistent TTX-sensitive sodium current and a ruthenium red-sensitive, TRP-like cationic current, both of which are active during interspike intervals and have reversal potentials positive to threshold. Interestingly, although UBCs are also endowed with a large Ih current, this current is not involved in their intrinsic firing, perhaps because it activates at voltages that are more hyperpolarized than those associated with autonomous activity. [source] Stereospecific activity of two glutamate analogsCHIRALITY, Issue 9 2004Juan Manuel Araujo Alvarez Abstract Two glutamic acid analogs, (+)-(S)- and (,)-(R)-4-(2,2-diphenyl-1,3,2-oxazaborolidin-5-oxo)propionic acid ((+)-(S)- and (,)-(R)-Trujillon, respectively), were prepared. The stereospecific activity of their pharmacological properties was studied. The median convulsant dose (CD50) and median lethal dose (LD50) were analyzed in female Swiss Webster mice and their effects in vivo on unitary electrical activity in globus pallidus neurons were elucidated in male Wistar rats. Compounds were characterized by 1H, 13C, and 11B nuclear magnetic resonance. The LD50 of (+)-(S)-Trujillon was 449.08 mg/kg and it increased spontaneous motor activity, while with (,)-(R)-Trujillon there was no mortality up to 1,000 mg/kg and it decreased spontaneous motor activity. The CD50 in experiments with (+)-(S)-Trujillon was 199.34 mg/kg. Unitary recording in globus pallidus neurons showed i.v. administration (+)-(S)-Trujillon (50 mg/kg) increased frequency 79.0 ± 23.0% in relation to basal response. (,)-(R)-Trujillon and (+)-(S)-glutamate (50 mg/kg each) did not provoke changes in spontaneous basal firing. Local infusion of (+)-(S)-Trujillon (1 nMol) increased spontaneous firing in most neurons tested by 269.0 ± 83.0% in relation to basal values. Intrapallidal infusion of (,)-(R)-Trujillon (1 nMol) and saline solution did not cause statistically significant changes in globus pallidus spiking. Results showed that (+)-(S)-Trujillon crosses the blood,brain barrier and has stereospecific activity. Chirality 16:586,591, 2004. © 2004 Wiley-Liss, Inc. [source] | |||||||||||||