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Calcium channel gating and modulation by transmitters depend on cellular compartmentalization

Abstract

Voltage-gated Ca2+ channels participate in dendritic integration, yet functional properties of Ca2+ channels and mechanisms of their modulation by neurotransmitters in dendrites are unknown. Here we report how pharmacologically identified Ca2+ channels behave in different neural compartments. Whole-cell and cell-attached patch-clamp recordings were made on both cell bodies and electrically isolated dendrites of sympathetic neurons. We found not only that Ca2+ channel populations differentially contribute to somatic and dendritic currents but also that families of Ca2+ channels display gating properties and neurotransmitter modulation that depend on channel compartmentalization. By comparison with their somatic counterparts, dendritic N-type Ca2+ currents were hypersensitive to neurotransmitters and G proteins. Single-channel analysis showed that dendrites express a unique N-type channel that has enhanced interaction with Gβγ. Thus Ca2+ channels in dendrites seem to be specialized elements with unique regulatory mechanisms.

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Figure 1: Calcium current recordings in processes of sympathetic neurons.
Figure 2: Components of the Ca2+ current in dendrites.
Figure 3: N-type Ca2+ current in dendrites is hypersensitive to neurotransmitters.
Figure 4: Time course of re-inhibition and relief from inhibition are different in dendrite and soma.
Figure 5: Two groups of Ca2+ channel conductances in dendrite and soma.
Figure 6: High- and low-conductance Ca2+ channels are blocked by ω-CgTx GVIA.
Figure 7: Prepulse facilitation of large but not small ω-CgTx GVIA-sensitive channels.

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Acknowledgements

We thank M. Dayrell for technical assistance and G. Milligan for the gift of Gα-transducin, Gβ1 and Gγ2 cDNAs. This work was supported by The Wellcome Trust.

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Correspondence to Patrick Delmas.

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Delmas, P., Abogadie, F., Buckley, N. et al. Calcium channel gating and modulation by transmitters depend on cellular compartmentalization. Nat Neurosci 3, 670–678 (2000). https://doi.org/10.1038/76621

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