PUBLICATION
Zebrafish CaV2.1 Calcium Channels Are Tailored for Fast Synchronous Neuromuscular Transmission
- Authors
- Naranjo, D., Wen, H., Brehm, P.
- ID
- ZDB-PUB-150205-5
- Date
- 2015
- Source
- Biophysical journal 108: 578-584 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Rats
- Calcium Channels, N-Type/metabolism*
- Motor Neurons/physiology
- HEK293 Cells
- Humans
- Action Potentials/physiology
- Ion Channel Gating/physiology
- Synaptic Transmission/physiology*
- Zebrafish/metabolism*
- Animals
- Time Factors
- Neuromuscular Junction/physiology*
- PubMed
- 25650925 Full text @ Biophys. J.
Citation
Naranjo, D., Wen, H., Brehm, P. (2015) Zebrafish CaV2.1 Calcium Channels Are Tailored for Fast Synchronous Neuromuscular Transmission. Biophysical journal. 108:578-584.
Abstract
The CaV2.2 (N-type) and CaV2.1 (P/Q-type) voltage-dependent calcium channels are prevalent throughout the nervous system where they mediate synaptic transmission, but the basis for the selective presence at individual synapses still remains an open question. The CaV2.1 channels have been proposed to respond more effectively to brief action potentials (APs), an idea supported by computational modeling. However, the side-by-side comparison of CaV2.1 and CaV2.2 kinetics in intact neurons failed to reveal differences. As an alternative means for direct functional comparison we expressed zebrafish CaV2.1 and CaV2.2 α-subunits, along with their accessory subunits, in HEK293 cells. HEK cells lack calcium currents, thereby circumventing the need for pharmacological inhibition of mixed calcium channel isoforms present in neurons. HEK cells also have a simplified morphology compared to neurons, which improves voltage control. Our measurements revealed faster kinetics and shallower voltage-dependence of activation and deactivation for CaV2.1. Additionally, recordings of calcium current in response to a command waveform based on the motorneuron AP show, directly, more effective activation of CaV2.1. Analysis of calcium currents associated with the AP waveform indicate an approximately fourfold greater open probability (PO) for CaV2.1. The efficient activation of CaV2.1 channels during APs may contribute to the highly reliable transmission at zebrafish neuromuscular junctions.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping