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Pacemaker Activity (pacemaker + activity)
Selected AbstractsSustained Inward Current and Pacemaker Activity of Mammalian Sinoatrial NodeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2002HENGGUI ZHANG Ph.D. Sustained Inward Current in the Sinoatrial Node.Introduction: A novel sustained inward Na+ current ist, which sensitive to Ca2+ -antagonists and potentiated by beta-adrenergic stimulation, has been described in pacemaker cells of rabbit, guinea pig, and rat sinoatrial node, as well as rabbit AV node. Although ist has been suggested to be an important pacemaker current, this has never been tested experimentally because of the lack of a specific blocker. In this study, we address the role of ist in the pacemaker activity of the sinoatrial node cell using computer models. Methods and Results: The newly developed models of Zhang et al. for peripheral and central rabbit sinoatrial node cells and models of Noble and Noble, Demir et al., Wilders et al., and Dokos et al. for typical rabbit sinoatrial node cells were modified to incorporate equations for ist. The conductance gst was chosen to give a current density-voltage relationship consistent with experimental data. In the models of Zhang et al. (periphery), Noble and Noble, and Dokos et al., in which ist was smaller or about the same amplitude as other inward currents, ist increased the pacemaking rate by 0.6%, 2.2%, and 0.8%, respectively. In the models of Zhang et al. (center), Demir et al., and Wilders et al., in which ist was larger than some other inward ionic currents, ist increased the pacemaking rate by 7%, 20%, and 14%, respectively. Conclusion: ist has the potential to be a regulator of pacemaker activity, although its importance will depend on the amplitude of ist relative to the amplitude of other inward currents involved in pacemaker activity. [source] The contribution of the intrinsic excitability of vestibular nucleus neurons to recovery from vestibular damageEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2002Cynthia L. Darlington Abstract Damage to the peripheral vestibular system results in a syndrome of ocular motor and postural abnormalities that partially and gradually abate over time in a process known as ,vestibular compensation'. The first, rapid, phase of compensation has been associated with a recovery of spontaneous resting activity in the ipsilateral vestibular nucleus complex (VNC), as a consequence of neuronal and synaptic plasticity. Increasing evidence suggests that normal VNC neurons in labyrinthine-intact animals, as well as ipsilateral VNC neurons following unilateral vestibular deafferentation (UVD), rely to some extent on intrinsic pacemaker activity provided by voltage-dependent conductances for their resting activity. Modification of this intrinsic pacemaker activity may underlie the recovery of resting activity that occurs in ipsilateral VNC neurons following UVD. This review summarizes and critically evaluates the ,intrinsic mechanism hypothesis', identifying discrepancies amongst the current evidence and suggesting experiments that may test it further. [source] Endothelin-1 Modulates the Arrhythmogenic Activity of Pulmonary VeinsJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 3 2008AMEYA R. UDYAVAR M.D. Objective: Endothelin-1 has important cardiovascular effects and is activated during atrial fibrillation. Pulmonary veins (PVs) play a critical role in the pathophysiology of atrial fibrillation. The aim of this study was to evaluate whether endothelin-1 affects PV arrhythmogenic activity. Methods: Conventional microelectrodes were used to record the action potentials (APs) and contractility in isolated rabbit PV tissue specimens before and after the administration of endothelin-1 (0.1, 1, 10 nM). The ionic currents of isolated PV cardiomyocytes were investigated before and after the administration of endothelin-1 (10 nM) through whole-cell patch clamps. Results: In the tissue preparation, endothelin-1 (1, 10 nM) concentration dependently shortened the AP duration and decreased the PV firing rates. Endothelin-1 (10 nM) decreased the resting membrane potential. Endothelin-1 (0.1, 1, 10 nM) decreased the contractility and increased the resting diastolic tension. In single PV cardiomyocytes, endothelin-1 (10 nM) decreased the PV firing rates from 2.7 ± 1.0 Hz to 0.8 ± 0.5 Hz (n = 16). BQ-485 (100 ,M, endothelin-1 type A receptor blocker) reversed and prevented the chrono-inhibitory effects of endothelin-1 (10 nM). Endothelin-1 (10 nM) reduced the L-type calcium currents, transient outward currents, delayed rectifier currents, transient inward currents, and sodium,calcium exchanger currents in the PV cardiomyocytes with and without pacemaker activity. Endothelin-1 (10 nM) increased the inward rectifier potassium current, hyperpolarization-induced pacemaker current, and the sustained outward potassium current in PV cardiomyocytes with and without pacemaker activity. Conclusion: Endothelin-1 may have an antiarrhythmic potential through its direct electrophysiological effects on the PV cardiomyocytes and its action on multiple ionic currents. [source] Sustained Inward Current and Pacemaker Activity of Mammalian Sinoatrial NodeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2002HENGGUI ZHANG Ph.D. Sustained Inward Current in the Sinoatrial Node.Introduction: A novel sustained inward Na+ current ist, which sensitive to Ca2+ -antagonists and potentiated by beta-adrenergic stimulation, has been described in pacemaker cells of rabbit, guinea pig, and rat sinoatrial node, as well as rabbit AV node. Although ist has been suggested to be an important pacemaker current, this has never been tested experimentally because of the lack of a specific blocker. In this study, we address the role of ist in the pacemaker activity of the sinoatrial node cell using computer models. Methods and Results: The newly developed models of Zhang et al. for peripheral and central rabbit sinoatrial node cells and models of Noble and Noble, Demir et al., Wilders et al., and Dokos et al. for typical rabbit sinoatrial node cells were modified to incorporate equations for ist. The conductance gst was chosen to give a current density-voltage relationship consistent with experimental data. In the models of Zhang et al. (periphery), Noble and Noble, and Dokos et al., in which ist was smaller or about the same amplitude as other inward currents, ist increased the pacemaking rate by 0.6%, 2.2%, and 0.8%, respectively. In the models of Zhang et al. (center), Demir et al., and Wilders et al., in which ist was larger than some other inward ionic currents, ist increased the pacemaking rate by 7%, 20%, and 14%, respectively. Conclusion: ist has the potential to be a regulator of pacemaker activity, although its importance will depend on the amplitude of ist relative to the amplitude of other inward currents involved in pacemaker activity. [source] Gonadotrophin-Releasing Hormone Pulse Generator Activity in the Hypothalamus of the GoatJOURNAL OF NEUROENDOCRINOLOGY, Issue 10 2009S. Ohkura Pulsatile release of gonadotrophin-releasing hormone (GnRH) is indispensable to maintain normal gonadotrophin secretion. The pulsatile secretion of GnRH is associated with synchronised electrical activity in the mediobasal hypothalamus (i.e. multiple unit activity; MUA), which is considered to reflect the rhythmic oscillations in the activity of the neuronal network that drives pulsatile GnRH secretion. However, the cellular source of this ultradian rhythm in GnRH activity is unknown. Direct input from kisspeptin neurones in the arcuate nucleus (ARC) to GnRH cell bodies in the medial preoptic area or their terminals in the median eminence could be the intrinsic source for driving the GnRH pulse generator. To determine whether kisspeptin signalling could be responsible for producing pulsatile GnRH secretion, we studied goats, measured plasma levels of luteinising hormone (LH) and recorded MUA in the posterior ARC, where the majority of kisspeptin neuronal cell bodies are located. Rhythmic volleys of MUA were found to be accompanied by LH pulses with regular intervals in the ARC, where kisspeptin neuronal cell bodies were found. Exogenous administration of kisspeptin stimulated a sustained increase in LH secretion, without influencing MUA, suggesting that the GnRH pulse generator, as reflected by MUA, originated from outside of the network of GnRH neurones, and could plausibly reflect the pacemaker activity of kisspeptin neurones, whose projections reach the median eminence where GnRH fibres project. These observations suggest that the kisspeptin neurones in the ARC may be the intrinsic source of the GnRH pulse generator. [source] Immunohistochemical localization of Ih channel subunits, HCN1,4, in the rat brainTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 3 2004Takuya Notomi Abstract Hyperpolarization-activated cation currents (Ih) contribute to various physiological properties and functions in the brain, including neuronal pacemaker activity, setting of resting membrane potential, and dendritic integration of synaptic input. Four subunits of the Hyperpolarization-activated and Cyclic-Nucleotide-gated nonselective cation channels (HCN1,4), which generate Ih, have been cloned recently. To better understand the functional diversity of Ih in the brain, we examined precise immunohistochemical localization of four HCNs in the rat brain. Immunoreactivity for HCN1 showed predominantly cortical distribution, being intense in the neocortex, hippocampus, superior colliculus, and cerebellum, whereas those for HCN3 and HCN4 exhibited subcortical distribution mainly concentrated in the hypothalamus and thalamus, respectively. Immunoreactivity for HCN2 had a widespread distribution throughout the brain. Double immunofluorescence revealed colocalization of immunoreactivity for HCN1 and HCN2 in distal dendrites of pyramidal cells in the hippocampus and neocortex. At the electron microscopic level, immunogold particles for HCN1 and HCN2 had similar distribution patterns along plasma membrane of dendritic shafts in layer I of the neocortex and stratum lacunosum moleculare of the hippocampal CA1 area, suggesting that these subunits could form heteromeric channels. Our results further indicate that HCNs are localized not only in somato-dendritic compartments but also in axonal compartments of neurons. Immunoreactivity for HCNs often occurred in preterminal rather than terminal portions of axons and in specific populations of myelinated axons. We also found HCN2-immunopositive oligodendrocytes including perineuronal oligodendrocytes throughout the brain. These results support previous electrophysiological findings and further suggest unexpected roles of Ih channels in the brain. J. Comp. Neurol. 471:241,276, 2004. © 2004 Wiley-Liss, Inc. [source] Role of mitochondria in modulation of spontaneous Ca2+ waves in freshly dispersed interstitial cells of Cajal from the rabbit urethraTHE JOURNAL OF PHYSIOLOGY, Issue 19 2008Gerard P. Sergeant Interstitial cells of Cajal (ICC) isolated from the rabbit urethra exhibit pacemaker activity that results from spontaneous Ca2+ waves. The purpose of this study was to investigate if this activity was influenced by Ca2+ uptake into mitochondria. Spontaneous Ca2+ waves were recorded using a Nipkow spinning disk confocal microscope and spontaneous transient inward currents (STICs) were recorded using the whole-cell patch clamp technique. Disruption of the mitochondrial membrane potential with the electron transport chain inhibitors rotenone (10 ,m) and antimycin A (5 ,m) abolished Ca2+ waves and increased basal Ca2+ levels. Similar results were achieved when mitochondria membrane potential was collapsed using the protonophores FCCP (0.2 ,m) and CCCP (1 ,m). Spontaneous Ca2+ waves were not inhibited by the ATP synthase inhibitor oligomycin (1 ,m), suggesting that these effects were not attributable to an effect on ATP levels. STICs recorded under voltage clamp at ,60 mV were also inhibited by CCCP and antimycin A. Dialysis of cells with the mitochondrial uniporter inhibitor RU360 (10 ,m) also inhibited STICS. Stimulation of Ca2+ uptake into mitochondria using the plant flavonoid kaempferol (10 ,m) induced a series of propagating Ca2+ waves. The kaempferol-induced activity was inhibited by application of caffeine (10 mm) or removal of extracellular Ca2+, but was not significantly affected by the IP3 receptor blocker 2-APB (100 ,m). These data suggest that spontaneous Ca2+ waves in urethral ICC are regulated by buffering of cytoplasmic Ca2+ by mitochondria. [source] Atypical slow waves generated in gastric corpus provide dominant pacemaker activity in guinea pig stomachTHE JOURNAL OF PHYSIOLOGY, Issue 2 2005Hikaru Hashitani When intracellular recordings were made from the circular layer of the intact muscular wall of the isolated guinea pig gastric corpus, an ongoing regular high frequency discharge of slow waves was detected even though this region lacked myenteric interstitial cells. When slow waves were recorded from preparations consisting of both the antrum and the corpus, slow waves of identical frequency, but with different shapes, were generated in the two regions. Corporal slow waves could be distinguished from antral slow waves by their time courses and amplitudes. Corporal slow waves, like antral slow waves, were abolished by buffering the internal concentration of calcium ions, [Ca2+]i, to low levels, or by caffeine, 2-aminoethoxydiphenyl borate or the chloride channel blocker DIDS. Corporal preparations demonstrated an ongoing discharge of unitary potentials, as has been found in all other tissues containing interstitial cells. The experiments show that the corpus provides the dominant pacemaker activity which entrains activity in other regions of the stomach and it is suggested that this activity is generated by corporal intramuscular interstitial cells. [source] | |||||||||||||