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Agrin mediates a rapid switch from electrical coupling to chemical neurotransmission during synaptogenesis.

Martin AO, Alonso G, Guérineau NC - J. Cell Biol. (2005)

Bottom Line: When applied at the developing splanchnic nerve-chromaffin cell cholinergic synapse in rat adrenal acute slices, agrin rapidly modified cell-to-cell communication mechanisms.This developmental switch from predominantly electrical to chemical communication was fully operational within one hour and depended on the activation of Src family-related tyrosine kinases.Hence, agrin may play a pivotal role in synaptogenesis in promoting a rapid switch between electrical coupling and synaptic neurotransmission.

View Article: PubMed Central - PubMed

Affiliation: CNRS UMR5203, INSERM U661, Université Montpellier I, Département d'Endocrinologie, Institut de Génomique Fonctionnelle, 34094 Montpellier Cedex 5, France.

ABSTRACT
In contrast to its well-established actions as an organizer of synaptic differentiation at the neuromuscular junction, the proteoglycan agrin is still in search of a function in the nervous system. Here, we report an entirely unanticipated role for agrin in the dual modulation of electrical and chemical intercellular communication that occurs during the critical period of synapse formation. When applied at the developing splanchnic nerve-chromaffin cell cholinergic synapse in rat adrenal acute slices, agrin rapidly modified cell-to-cell communication mechanisms. Specifically, it led to decreased gap junction-mediated electrical coupling that preceded an increase in nicotinic synaptic transmission. This developmental switch from predominantly electrical to chemical communication was fully operational within one hour and depended on the activation of Src family-related tyrosine kinases. Hence, agrin may play a pivotal role in synaptogenesis in promoting a rapid switch between electrical coupling and synaptic neurotransmission.

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Related in: MedlinePlus

Agrin-evoked rapid decrease in Ij. (A) Ij was continuously monitored in a neonatal chromaffin cell pair voltage- clamped at −60 mV. A voltage step (60 mV, 150 ms) was elicited every 30 s. Bath-applied agrin (50 ng/ml, 10 min) reduced Ij amplitude by ∼60% within a few minutes. (B) Pooled data showing that a 10-min agrin exposure irreversibly reduced Ij amplitude by 50%, with a maximal effect within 6 min.
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fig6: Agrin-evoked rapid decrease in Ij. (A) Ij was continuously monitored in a neonatal chromaffin cell pair voltage- clamped at −60 mV. A voltage step (60 mV, 150 ms) was elicited every 30 s. Bath-applied agrin (50 ng/ml, 10 min) reduced Ij amplitude by ∼60% within a few minutes. (B) Pooled data showing that a 10-min agrin exposure irreversibly reduced Ij amplitude by 50%, with a maximal effect within 6 min.

Mentions: As a first step toward the characterization of mechanisms involved in agrin-induced changes in cell-to-cell communication, we investigated the time course of agrin effects on both electrical coupling and synaptic nicotinic transmission. Ij was continuously monitored before and during 10 min bath-applied agrin (50 ng/ml). As illustrated in Fig. 6 A, Ij amplitude rapidly and dramatically decreased upon agrin application, with a maximal effect observed within 5–6 min (n = 6/6 cell pairs). Pooled data show that a 10-min exposure to agrin reduced Ij amplitude by ∼50% (range from 15 to 63%), whereas it remained unchanged in control saline (Fig. 6 B, n = 13 cell pairs). Regarding synaptic transmission, a statistically significant increase in sEPSC amplitude was observed after 45–60 min of continuously applied agrin (Fig. 7). These results clearly indicate that (1) the effect of agrin on the two intercellular communication modes is sequential, i.e., the reduction of gap junctional communication precedes the increase of synaptic neurotransmission; and (2) the switch between electrical and chemical coupling occurs rapidly and is fully operational within 1 h.


Agrin mediates a rapid switch from electrical coupling to chemical neurotransmission during synaptogenesis.

Martin AO, Alonso G, Guérineau NC - J. Cell Biol. (2005)

Agrin-evoked rapid decrease in Ij. (A) Ij was continuously monitored in a neonatal chromaffin cell pair voltage- clamped at −60 mV. A voltage step (60 mV, 150 ms) was elicited every 30 s. Bath-applied agrin (50 ng/ml, 10 min) reduced Ij amplitude by ∼60% within a few minutes. (B) Pooled data showing that a 10-min agrin exposure irreversibly reduced Ij amplitude by 50%, with a maximal effect within 6 min.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171940&req=5

fig6: Agrin-evoked rapid decrease in Ij. (A) Ij was continuously monitored in a neonatal chromaffin cell pair voltage- clamped at −60 mV. A voltage step (60 mV, 150 ms) was elicited every 30 s. Bath-applied agrin (50 ng/ml, 10 min) reduced Ij amplitude by ∼60% within a few minutes. (B) Pooled data showing that a 10-min agrin exposure irreversibly reduced Ij amplitude by 50%, with a maximal effect within 6 min.
Mentions: As a first step toward the characterization of mechanisms involved in agrin-induced changes in cell-to-cell communication, we investigated the time course of agrin effects on both electrical coupling and synaptic nicotinic transmission. Ij was continuously monitored before and during 10 min bath-applied agrin (50 ng/ml). As illustrated in Fig. 6 A, Ij amplitude rapidly and dramatically decreased upon agrin application, with a maximal effect observed within 5–6 min (n = 6/6 cell pairs). Pooled data show that a 10-min exposure to agrin reduced Ij amplitude by ∼50% (range from 15 to 63%), whereas it remained unchanged in control saline (Fig. 6 B, n = 13 cell pairs). Regarding synaptic transmission, a statistically significant increase in sEPSC amplitude was observed after 45–60 min of continuously applied agrin (Fig. 7). These results clearly indicate that (1) the effect of agrin on the two intercellular communication modes is sequential, i.e., the reduction of gap junctional communication precedes the increase of synaptic neurotransmission; and (2) the switch between electrical and chemical coupling occurs rapidly and is fully operational within 1 h.

Bottom Line: When applied at the developing splanchnic nerve-chromaffin cell cholinergic synapse in rat adrenal acute slices, agrin rapidly modified cell-to-cell communication mechanisms.This developmental switch from predominantly electrical to chemical communication was fully operational within one hour and depended on the activation of Src family-related tyrosine kinases.Hence, agrin may play a pivotal role in synaptogenesis in promoting a rapid switch between electrical coupling and synaptic neurotransmission.

View Article: PubMed Central - PubMed

Affiliation: CNRS UMR5203, INSERM U661, Université Montpellier I, Département d'Endocrinologie, Institut de Génomique Fonctionnelle, 34094 Montpellier Cedex 5, France.

ABSTRACT
In contrast to its well-established actions as an organizer of synaptic differentiation at the neuromuscular junction, the proteoglycan agrin is still in search of a function in the nervous system. Here, we report an entirely unanticipated role for agrin in the dual modulation of electrical and chemical intercellular communication that occurs during the critical period of synapse formation. When applied at the developing splanchnic nerve-chromaffin cell cholinergic synapse in rat adrenal acute slices, agrin rapidly modified cell-to-cell communication mechanisms. Specifically, it led to decreased gap junction-mediated electrical coupling that preceded an increase in nicotinic synaptic transmission. This developmental switch from predominantly electrical to chemical communication was fully operational within one hour and depended on the activation of Src family-related tyrosine kinases. Hence, agrin may play a pivotal role in synaptogenesis in promoting a rapid switch between electrical coupling and synaptic neurotransmission.

Show MeSH
Related in: MedlinePlus