Stimulation of bursting in pre‐Bötzinger neurons by Epac through calcium release and modulation of TRPM4 and K‐ATP channels

Mironov, S. L.; Skorova, E.

doi:10.1111/j.1471-4159.2011.07202.x

Cited by 37 publications

(30 citation statements)

References 49 publications

(121 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Synaptic depression is a possible mechanism that would halt recurrent excitation (Rubin et al 2009a). Burst termination may also involve “activity-dependent” outward currents evoked by intense spiking, including: Na + /K + ATPase electrogenic pump current, Na + -dependent K + current, and ATP-dependent K + channels (Del Negro et al 2009, Haller et al 2001, Krey et al 2010, Mironov et al 1998, Mironov & Skorova 2011). …”

Section: Prebötzinger Complex and Inspirationmentioning

confidence: 99%

“…Somatic Ca 2+ transients, on the other hand, do not appear to play a critical role (Morgado-Valle et al 2008). The underlying ion channels appear to be members of the transient receptor potential ( trp ) family, most likely TRPM4 or TRPM5 (Crowder et al 2007, Mironov 2008, Mironov & Skorova 2011), or possibly TRPC3 or TRPC7 (Ben-Mabrouk & Tryba 2010). Dendritic excitability is critically important in understanding neuron computation in general (London & Hausser 2005, Stuart et al 2007).…”

Section: Prebötzinger Complex and Inspirationmentioning

confidence: 99%

See 1 more Smart Citation

Understanding the Rhythm of Breathing: So Near, Yet So Far

Feldman

Negro

Gray

2013

Annu. Rev. Physiol.

392

362

View full text Add to dashboard Cite

Understanding the mechanisms leading from DNA to molecules to neurons to networks to behavior is a major goal for neuroscience, but largely out of reach for many fundamental and interesting behaviors. The neural control of breathing may be a rare exception, presenting a unique opportunity to understand how the nervous system functions normally, how it balances inherent robustness with a highly regulated lability, how it adapts to rapidly and slowly changing conditions, and how particular dysfunctions result in disease. Why can we assert this? First and foremost, the functions of breathing are clearly definable, starting with its regulatory job of maintaining blood (and brain) O2, CO2 and pH; failure is not an option. Breathing is also an essential component of many vocal and emotive behaviors including, e.g., crying, laughing, singing, and sniffing, and must be coordinated with such vital behaviors as suckling and swallowing, even at birth. Second, the regulated variables, O2, CO2 and pH (and temperature in non-primate mammals), are continuous and are readily and precisely quantifiable, as is ventilation itself along with the underlying rhythmic motor activity, i.e., respiratory muscle EMGs. Third, we breathe all the time, except for short breaks as during breath-holding (which can be especially long in diving or hibernating mammals) or sleep apnea. Mammals (including humans) breathe in all behavioral states, e.g., sleep-wake, rest, exercise, panic, or fear, during anesthesia and even following decerebration. Moreover, essential aspects of the neural mechanisms driving breathing, including rhythmicity, are present at levels of reduction down to a medullary slice. Fourth, the relevant circuits exhibit a remarkable combination of extraordinary reliability, starting ex utero with the first air breath – intermittent breathing movements actually start in utero during the third trimester – and continuing for as many as ~109 breaths, as well as considerable lability, responding rapidly (in less than one second) and with considerable precision, over an order of magnitude in metabolic demand for O2 (~0.25 to ~5 liters of O2/min). Breathing does indeed persist! Finally, breathing is genetically determined to work at birth, with a well-defined developmental program underlying a neuroanatomical organization with apparent segregation of function, i.e., rhythmogenesis is separate from motor pattern (burst shape and coordination) generation. Importantly, single human gene mutations can affect breathing, and several neurodegenerative disorders compromise breathing by direct effects on brainstem respiratory circuits (See below).

show abstract

Section: Prebötzinger Complex and Inspirationmentioning

confidence: 99%

Section: Prebötzinger Complex and Inspirationmentioning

confidence: 99%

Understanding the Rhythm of Breathing: So Near, Yet So Far

Feldman

Negro

Gray

2013

Annu. Rev. Physiol.

392

362

View full text Add to dashboard Cite

show abstract

“…The clearest role of TRPM5 is in taste transduction as mice with a targeted deletion of TRPM5 have little or no ability to detect physiologically relevant concentrations of bitter or sweet tastants (Zhang et al, 2003; Damak et al, 2006). In addition, based solely on its expression pattern, two studies have suggested that these channels may also contribute to the sADP in respiratory neurons of the pre-Botzinger complex (Mironov, 2008; Mironov and Skorova, 2011). However, the role of TRPM4 and TRPM5 in the central nervous system remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Differential contribution of TRPM4 and TRPM5 nonselective cation channels to the slow afterdepolarization in mouse prefrontal cortex neurons

Lei

Thuault

Launay

et al. 2014

Front. Cell. Neurosci.

View full text Add to dashboard Cite

In certain neurons from different brain regions, a brief burst of action potentials can activate a slow afterdepolarization (sADP) in the presence of muscarinic acetylcholine receptor agonists. The sADP, if suprathreshold, can contribute to persistent non-accommodating firing in some of these neurons. Previous studies have characterized a Ca2+-activated non-selective cation (CAN) current (ICAN) that is thought to underlie the sADP. ICAN depends on muscarinic receptor stimulation and exhibits a dependence on neuronal activity, membrane depolarization and Ca2+-influx similar to that observed for the sADP. Despite the widespread occurrence of sADPs in neurons throughout the brain, the molecular identity of the ion channels underlying these events, as well as ICAN, remains uncertain. Here we used a combination of genetic, pharmacological and electrophysiological approaches to characterize the molecular mechanisms underlying the muscarinic receptor-dependent sADP in layer 5 pyramidal neurons of mouse prefrontal cortex. First, we confirmed that in the presence of the cholinergic agonist carbachol a brief burst of action potentials triggers a prominent sADP in these neurons. Second, we confirmed that this sADP requires activation of a PLC signaling cascade and intracellular calcium signaling. Third, we obtained direct evidence that the transient receptor potential (TRP) melastatin 5 channel (TRPM5), which is thought to function as a CAN channel in non-neural cells, contributes importantly to the sADP in the layer 5 neurons. In contrast, the closely related TRPM4 channel may play only a minor role in the sADP.

show abstract

“…The increased level of TRPM4 channels has been reported in vascular endothelium following hypoxia/ischemia, in the endothelial cells of capillary vessels following spinal cord injury [[26],[27]]. In the brain, expression and/or channel activities of TRPM4 have been detected in hippocampus, cerebellar Purkinje cells, preBӧtzinger complex in the brainstem, magnocellular cells in supraoptic and paraventricular nuclei, and substantia nigra pars compacta [[28]-[32]]. Recently, TRPM4 has been shown to be important in neuronal cell death of experimental autoimmune encephalomyelitis and human multiple sclerosis tissues [[31]].…”

Section: Introductionmentioning

confidence: 99%

Depletion of 14-3-3γ reduces the surface expression of Transient Receptor Potential Melastatin 4b (TRPM4b) Channels and attenuates TRPM4b-mediated glutamate-induced neuronal cell death

et al. 2014

View full text Add to dashboard Cite

BackgroundTRPM4 channels are Ca2+-activated nonselective cation channels which are deeply involved in physiological and pathological conditions. However, their trafficking mechanism and binding partners are still elusive.ResultsWe have found the 14-3-3γ as a binding partner for TRPM4b using its N-terminal fragment from the yeast-two hybrid screening. Ser88 at the N-terminus of TRPM4b is critical for 14-3-3γ binding by showing GST pull-down and co-immunoprecipitation. Heterologous overexpression of 14-3-3γ in HEK293T cells increased TRPM4b expression on the plasma membrane which was measured by whole-cell recordings and cell surface biotinylation experiment. Surface expression of TRPM4b was greatly reduced by short hairpin RNA (shRNA) against 14-3-3γ. Next, endogenous TRPM4b-mediated currents were electrophysiologically characterized by application of glutamate and 9-phenanthrol, a TRPM4b specific antagonist in HT-22 cells which originated from mouse hippocampal neurons. Glutamate-induced TRPM4b currents were significantly attenuated by shRNAs against 14-3-3γ or TRPM4b in these cells. Finally, glutamate-induced cell death was greatly prevented by treatment of 9-phenanthrol or 14-3-3γ shRNA.ConclusionThese results showed that the cell surface expression of TRPM4 channels is mediated by 14-3-3γ binding, and the specific inhibition of this trafficking process can be a potential therapeutic target for glutamate-induced neuronal cell death.

show abstract

Stimulation of bursting in pre‐Bötzinger neurons by Epac through calcium release and modulation of TRPM4 and K‐ATP channels

Cited by 37 publications

References 49 publications

Understanding the Rhythm of Breathing: So Near, Yet So Far

Understanding the Rhythm of Breathing: So Near, Yet So Far

Differential contribution of TRPM4 and TRPM5 nonselective cation channels to the slow afterdepolarization in mouse prefrontal cortex neurons

Depletion of 14-3-3γ reduces the surface expression of Transient Receptor Potential Melastatin 4b (TRPM4b) Channels and attenuates TRPM4b-mediated glutamate-induced neuronal cell death

Contact Info

Product

Resources

About