A Constitutive, Transient Receptor Potential-like Ca2+ Influx Pathway in Presynaptic Nerve Endings Independent of Voltage-gated Ca2+ Channels and Na+/Ca2+ Exchange

Nichols, Robert A.; Dengler, Andrew F.; Nakagawa, Emily M.; Bashkin, Marisa; Paul, Brian T.; Wu, Jianlin; Khan, Ghous M.

doi:10.1074/jbc.m706002200

Cited by 18 publications

(13 citation statements)

References 102 publications

(95 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with the role of the background Na ϩ current in the control of resting membrane potential, some TRPC channels are constitutively active (24,36). Furthermore, in interstitial cells of Cajal, TRPC4 was suggested as a molecular candidate for the nonselective cation channel responsible for the pacemaker activity (14).…”

Section: Discussionmentioning

confidence: 80%

Role of nonselective cation channels in spontaneous and protein kinase A-stimulated calcium signaling in pituitary cells

Tomić

Kučka

Kretschmannova

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

-Several receptors linked to the adenylyl cyclase signaling pathway stimulate electrical activity and calcium influx in endocrine pituitary cells, and a role for an unidentified sodium-conducting channel in this process has been proposed. Here we show that forskolin dose-dependently increases cAMP production and facilitates calcium influx in about 30% of rat and mouse pituitary cells at its maximal concentration. The stimulatory effect of forskolin on calcium influx was lost in cells with inhibited PKA (cAMP-dependent protein kinase) and in cells that were haploinsufficient for the main PKA regulatory subunit but was preserved in cells that were also haploinsufficient for the main PKA catalytic subunit. Spontaneous and forskolin-stimulated calcium influx was present in cells with inhibited voltage-gated sodium and hyperpolarization-activated cation channels but not in cells bathed in medium, in which sodium was replaced with organic cations. Consistent with the role of sodium-conducting nonselective cation channels in PKA-stimulated Ca 2ϩ influx, cAMP induced a slowly developing current with a reversal potential of about 0 mV. Two TRP (transient receptor potential) channel blockers, SKF96365 and 2-APB, as well as flufenamic acid, an inhibitor of nonselective cation channels, also inhibited spontaneous and forskolin-stimulated electrical activity and calcium influx. Quantitative RT-PCR analysis indicated the expression of mRNA transcripts for TRPC1 ϾϾ TRPC6 Ͼ TRPC4 Ͼ TRPC5 Ͼ TRPC3 in rat pituitary cells. These experiments suggest that in pituitary cells constitutively active cation channels are stimulated further by PKA and contribute to calcium signaling indirectly by controlling the pacemaking depolarization in a sodiumdependent manner and directly by conducting calcium.

show abstract

Section: Discussionmentioning

confidence: 80%

Role of nonselective cation channels in spontaneous and protein kinase A-stimulated calcium signaling in pituitary cells

Tomić

Kučka

Kretschmannova

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…La 3+ antagonizes several members of the canonical (C) family of TRP channels (TRPC3, 5, 6, and 7) (Albert et al, 2006), suggesting that PregS could act by potentiating these channels. TRPC channels have been found to be expressed in presynaptic nerve terminals (Goel et al, 2002, Nichols et al, 2007) and their activation has been implicated in neurotransmitter release modulation (Selvaraj et al). Interestingly, in the cerebellum, the expression of TRPC channels has been shown to be developmentally regulated; during the first 6 postnatal weeks, TRPC3 is abundantly expressed in comparison to TRPC4 and TRPC6 channels (Huang et al, 2007a).…”

Section: Discussionmentioning

confidence: 99%

Pregnenolone sulfate increases glutamate release at neonatal climbing fiber-to-Purkinje cell synapses

Zamudio-Bulcock

Valenzuela

2011

Neuroscience

View full text Add to dashboard Cite

Development of cerebellar Purkinje cells (PCs) is modulated by neuroactive steroids. Developing hippocampal pyramidal neurons retrogradely release a pregnenolone sulfate (PregS)-like neurosteroid that may contribute to glutamatergic synapse stabilization. We hypothesized that PregS could exert a similar effect on developing PCs. To test this hypothesis, we performed whole-cell patch-clamp recordings from PCs in acute cerebellar vermis slices from neonatal rats. PregS induced a robust (~3,000 %) and reversible increase in AMPA receptor-mediated miniature excitatory postsynaptic current (AMPA-mEPSC) frequency without affecting the amplitude, timeto-rise, or half-width of these events. PregS also increased the frequency of GABA A receptormediated miniature postsynaptic currents but to a significantly lesser extent (<100%). The PregSinduced increase of AMPA-mEPSC frequency was not significantly decreased by antagonists of receptors (NMDA, glycine, α7 nicotinic acetylcholine, and σ1) that have been shown to modulate glutamatergic transmission at PCs and/or mediate the actions of PregS on neurotransmitter release. Ca 2+ chelation experiments suggested that PregS acts by increasing presynaptic terminal [Ca 2+ ] i , an effect that is independent of voltage-gated Ca 2+ channels, but is blocked by the antagonist of transient receptor potential (TRP) channels, La 3+ . PregS also increased the amplitude of EPSCs evoked by climbing fiber (CF) stimulation and decreased the paired-pulse ratio of these events. Neither CF-nor parallel fiber-evoked EPSCs were affected by PregS in slices from juvenile rats. These results suggest that glutamate release at CF-to-PC synapses is an important target of PregS in the neonatal cerebellar cortex, an effect that may play a role in the refinement of these synapses.

show abstract

“…Cells were plated at low density onto Cell‐Tak‐coated coverslips in 35‐mm dishes and then differentiated with dibutyryl‐cyclic AMP (1 m m ) (Sigma‐Aldrich) in DMEM with 1% FBS. After 2–3 days, a pcDNA3.1 construct containing the mouse α7 nAChR sequence (courtesy of Dr Jerry Stitzel, University of Colorado) was transfected into differentiated cells using the transfectant reagent FuGENE 6 (Roche Diagnostics), obtaining typically > 80% transfection efficiency as previously described (Nichols et al. , 2007).…”

Section: Methodsmentioning

confidence: 99%

“…After 1–2 days, the transfected, differentiated cells were loaded with fluorescent Ca 2+ indicator dye Fluo‐4/AM (Invitrogen) at 5 μ m in HEPES‐buffered saline (HBS) containing (in m m ) 142 NaCl, 2.4 KCl, 1.2 K 2 PO 4 , 1 MgCl 2 , 1 CaCl 2 , 5 d ‐glucose, pH 7.4, and saturated with O 2 at 37°C for 1–1.5 h in preparation for confocal imaging, as described (Nichols et al. , 2007).…”

Section: Methodsmentioning

confidence: 99%

β‐Amyloid activates presynaptic α7 nicotinic acetylcholine receptors reconstituted into a model nerve cell system: involvement of lipid rafts

Khan

Tong

Jhun

et al. 2010

Eur J of Neuroscience

Self Cite

View full text Add to dashboard Cite

Beta amyloid (Abeta) plays a central role in the pathogenesis of Alzheimer's disease. Abeta is the major constituent of senile plaques, but there is a significant presence of Abeta in the brain in soluble forms. The results of functional studies indicate that soluble Abeta interacts with the alpha7 nicotinic acetylcholine receptor (nAChR) complex with apparent high affinity. However, conflicting data exist as to the nature of the Abeta-alpha7 nAChR interaction, and whether it is the result of specific binding. Moreover, both agonist-like and antagonist-like effects have been reported. In particular, agonist-like effects have been observed for presynaptic nAChRs. Here, we demonstrate Abeta(1-42)-evoked stimulatory changes in presynaptic Ca(2+) level via exogenous alpha7 nAChRs expressed in the axonal varicosities of differentiated hybrid neuroblastoma NG108-15 cells as a model, presynaptic system. The Abeta(1-42)-evoked responses were concentration-dependent and were sensitive to the highly selective alpha7 nAChR antagonist alpha-bungarotoxin. Voltage-gated Ca(2+) channels and internal Ca(2+) stores were both involved in Abeta(1-42)-evoked increases in presynaptic Ca(2+) following activation of alpha7 nAChRs. In addition, disruption of lipid rafts by cholesterol depletion led to substantially attenuated responses to Abeta(1-42), whereas responses to nicotine were largely intact. These results directly implicate the nicotinic receptor complex as a target for the agonist-like action of pico- to nanomolar concentrations of soluble Abeta(1-42) on the presynaptic nerve terminal, including the possible involvement of receptor-associated lipid rafts. This interaction probably plays an important neuromodulatory role in synaptic dynamics.

show abstract

A Constitutive, Transient Receptor Potential-like Ca2+ Influx Pathway in Presynaptic Nerve Endings Independent of Voltage-gated Ca2+ Channels and Na+/Ca2+ Exchange

Cited by 18 publications

References 102 publications

Role of nonselective cation channels in spontaneous and protein kinase A-stimulated calcium signaling in pituitary cells

Role of nonselective cation channels in spontaneous and protein kinase A-stimulated calcium signaling in pituitary cells

Pregnenolone sulfate increases glutamate release at neonatal climbing fiber-to-Purkinje cell synapses

β‐Amyloid activates presynaptic α7 nicotinic acetylcholine receptors reconstituted into a model nerve cell system: involvement of lipid rafts

Contact Info

Product

Resources

About