Dual mechanisms of angiotensin‐induced activation of mouse sympathetic neurones

Ma, Xiaojing; Bielefeldt, Klaus; Tan, ZC; Whiteis, Carol A.; Snitsarev, Vladislav; Abboud, François M.; Chapleau, Mark W.

doi:10.1113/jphysiol.2006.106716

Cited by 11 publications

(7 citation statements)

References 50 publications

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“…Yet the precise mechanisms underlying these behaviors are not well understood. AT1 receptors were detected in the lamina X, II, and VIII of the spinal cord, as well as in the IML (1,12,26). On this basis, we can speculate that the spinal cord neurons outside the IML are sensitive to ANG II.…”

Section: Discussionmentioning

confidence: 87%

Electrophysiological responses of sympathetic preganglionic neurons to ANG II and aldosterone

Minoura¹,

Onimaru²,

Iigaya³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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The intermediolateral cell column (IML) of the spinal cord is an important area where sympathetic impulses propagate to peripheral sympathetic organs. ANG II and aldosterone are important components of the renin-angiotensin-aldosterone system (RAAS), which activate the sympathetic nervous system. Each is partly synthesized in the brain and plays a paracrine role in the regulation of blood pressure independently of RAAS in the periphery. Our purpose in the present study was to clarify the contributions of sympathetic preganglionic neurons in the IML (IML neurons) and the effects of ANG II and aldosterone on the sympathetic nervous system. To examine responses to ANG II and aldosterone, we intracellularly recorded 104 IML neurons using a whole cell patch-clamp technique in spinal cord slice preparations. IML neurons were classified into two types: silent and firing. Both neuron types were significantly depolarized by ANG II, and candesartan inhibited this depolarization. After pretreatment with TTX, firing neurons (but not silent neurons) were significantly depolarized by ANG II. Aldosterone significantly increased the number of excitatory postsynaptic potentials (EPSPs) in both neuron types, but this response disappeared after pretreatment with TTX. ANG II and aldosterone had no synergistic effects on the IML neurons. The silent neurons had large cell soma, and many more dendrites than the firing neurons. These results suggest that ANG II acts presynaptically and postsynaptically in IML neurons, while aldosterone acts mainly presynaptically. Thus, the physiological effects of these substances are likely to be transmitted via specific membrane receptors of IML and/or presynaptic neurons.

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Section: Discussionmentioning

confidence: 87%

Electrophysiological responses of sympathetic preganglionic neurons to ANG II and aldosterone

Minoura¹,

Onimaru²,

Iigaya³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Similar results and conclusions to ours were obtained in comparable studies that evaluated the effects of other neurotransmitters/receptors, including activation of metabotropic glutamate receptors (Schrader & Tasker, ) and angiotensin II (Ma et al . ).…”

Section: Discussionmentioning

confidence: 97%

A functional coupling between extrasynaptic NMDA receptors and A‐type K⁺ channels under astrocyte control regulates hypothalamic neurosecretory neuronal activity

Naskar

Stern

2014

The Journal of Physiology

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Key pointsr In hypothalamic magnocellular neurosecretory cells, activation of glutamate NMDA receptors leads to inhibition of the transient voltage-gated A-type K + current (I A ), in a Ca 2+ -and protein kinase C-dependent manner.r The negative NMDAR-I A functional coupling involves activation of extrasynaptic (e)NMDARs.The eNMDAR-I A coupling is engaged by endogenous extracellular glutamate, whose levels are controlled by astrocyte glutamate GLT1 transporters.r The eNMDAR-I A coupling is enhanced during dehydration, a condition in which astrocyte GLT1 efficiency is blunted.r The eNMDAR-I A coupling results in increased neuronal excitability and firing activity in magnocellular neurosecretory neurons.r Taken together these studies support the concept that the eNMDAR-I A coupling is a powerful mechanism by which glutamate increases magnocellular neurosecretory excitability and firing activity.Abstract Neuronal activity is controlled by a fine-tuned balance between intrinsic properties and extrinsic synaptic inputs. Moreover, neighbouring astrocytes are now recognized to influence a wide spectrum of neuronal functions. Yet, how these three key factors act in concert to modulate and fine-tune neuronal output is not well understood. Here, we show that in rat hypothalamic magnocellular neurosecretory cells (MNCs), glutamate NMDA receptors (NMDARs) are negatively coupled to the transient, voltage-gated A-type K + current (I A ). We found that activation of NMDARs by extracellular glutamate levels influenced by astrocyte glutamate transporters resulted in a significant inhibition of I A . The NMDAR-I A functional coupling resulted from activation of extrasynaptic NMDARs, was calcium-and protein kinase C-dependent, and involved enhanced steady-state, voltage-dependent inactivation of I A . The NMDAR-I A coupling diminished the latency to the first evoked spike in response to membrane depolarization and increased the total number of evoked action potentials, thus strengthening the neuronal input/output function. Finally, we found a blunted NMDA-mediated inhibition of I A in dehydrated rats. Together, our findings support a novel signalling mechanism that involves a functional coupling between extrasynaptic NMDARs and A-type K + channels, which is influenced by local astrocytes. We show this signalling complex to play an important role in modulating hypothalamic neuronal excitability, which may contribute to adaptive responses during a sustained osmotic challenge such as dehydration.

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“…In vitro , several mechanisms have been identified that influence the excitability of sympathetic ganglion cells. Potassium channels underlying the M‐current and the afterhyperpolarization may be suppressed by angiotensin II (Ma et al 2006) and by muscarinic actions of acetylcholine (Adams et al 1982). Chloride channels open in response to increases in intracellular sodium, causing an activity‐related reduction in ganglion cell excitability (Sacchi et al 2003, 2007).…”

Section: Discussionmentioning

confidence: 99%

Ganglionic transmission in a vasomotor pathway studied in vivo

Bratton

Davies

Jänig

et al. 2010

The Journal of Physiology

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Intracellular recordings were made in vivo from 40 spontaneously active cells in the third lumbar sympathetic ganglion of urethane-anaesthetized rats. In 38/40 cells ongoing action potentials showed strong cardiac rhythmicity (93.4 ± 1.9% modulation) indicating high barosensitivity and probable muscle vasoconstrictor (MVC) function. Subthreshold excitatory postsynaptic potentials (EPSPs) showed the same pattern. The 38 barosensitive neurons fired action potentials at 2.9 ± 0.3 Hz. All action potentials were triggered by EPSPs, most of which were unitary events. Calculations indicated that <5% of action potentials were triggered by summation of otherwise subthreshold EPSPs. 'Dominant' synaptic inputs with a high safety factor were identified, confirming previous work. These were active in 24/38 cells and accounted for 32% of all action potentials; other ('secondary') inputs drove the remainder. Inputs (21 dominant, 19 secondary) attributed to single preganglionic neurons fired at 1.38 ± 0.16 Hz. An average of two to three preganglionic neurons were estimated to drive each ganglion cell's action potentials. When cells were held hyperpolarized to block spiking, a range of spontaneous EPSP amplitudes was revealed. Threshold equivalent was defined as the membrane potential value that was exceeded by spontaneous EPSPs at the same frequency as the cell's original firing rate. In 10/12 cells examined, a continuum of EPSP amplitudes overlapped threshold equivalent. Small changes in cell excitability could therefore raise or lower the percentage of preganglionic inputs triggering action potentials. The results indicate that vasoconstrictor ganglion cells in vivo mostly behave not as 1:1 relays, but as continuously variable gates.

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Dual mechanisms of angiotensin‐induced activation of mouse sympathetic neurones

Cited by 11 publications

References 50 publications

Electrophysiological responses of sympathetic preganglionic neurons to ANG II and aldosterone

Electrophysiological responses of sympathetic preganglionic neurons to ANG II and aldosterone

A functional coupling between extrasynaptic NMDA receptors and A‐type K⁺ channels under astrocyte control regulates hypothalamic neurosecretory neuronal activity

Ganglionic transmission in a vasomotor pathway studied in vivo

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Dual mechanisms of angiotensin‐induced activation of mouse sympathetic neurones

Cited by 11 publications

References 50 publications

Electrophysiological responses of sympathetic preganglionic neurons to ANG II and aldosterone

Electrophysiological responses of sympathetic preganglionic neurons to ANG II and aldosterone

A functional coupling between extrasynaptic NMDA receptors and A‐type K+ channels under astrocyte control regulates hypothalamic neurosecretory neuronal activity

Ganglionic transmission in a vasomotor pathway studied in vivo

Contact Info

Product

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A functional coupling between extrasynaptic NMDA receptors and A‐type K⁺ channels under astrocyte control regulates hypothalamic neurosecretory neuronal activity