Cav2 channels mediate low and high voltage-activated calcium currents in Drosophila motoneurons

Abstract

Key points Neurons in the brain express a diversity of ion channels to impart specialized functional properties. At least three distinct voltage gated calcium channel gene families are known, each of which is thought to produce calcium channels with unique properties, which in turn, differently affect neuronal function. Here we use a genetic model system to determine which genes are responsible for the calcium currents in an identified motoneuron. Surprisingly, the same ion channel gene encodes two distinct currents with fundamentally different properties, and the data also suggest that the normal function of this calcium channel gene is affected by the expression of another one. The results provide insights into the relationship between gene expression and ionic currents, and thus, into the regulation of normal neuronal function.

Autoren

Stefanie Ryglewski
Kimberly Lance
Richard B Levine
Carsten Duch

DOI

10.1113/jphysiol.2011.222836

eISSN

1469-7793

ISSN

0022-3751

Ausgabe der Veröffentlichung

4

Zeitschrift

The Journal of Physiology

Sprache

en

Online publication date

2012

Paginierung

809 - 825

Datum der Veröffentlichung

2012

Status

Published

Herausgeber

Wiley

Herausgeber URL

http://dx.doi.org/10.1113/jphysiol.2011.222836

Datum der Datenerfassung

2023

Titel

Ca<sub>v</sub>2 channels mediate low and high voltage‐activated calcium currents in <i>Drosophila</i> motoneurons

Ausgabe der Zeitschrift

590

Datenquelle: Crossref

Abstract

Different blends of membrane currents underlie distinct functions of neurons in the brain. A major step towards understanding neuronal function, therefore, is to identify the genes that encode different ionic currents. This study combined in situ patch clamp recordings of somatodendritic calcium currents in an identified adult Drosophila motoneuron with targeted genetic manipulation. Voltage clamp recordings revealed transient low voltage-activated (LVA) currents with activation between –60 mV and –70 mV as well as high voltage-activated (HVA) current with an activation voltage around –30 mV. LVA could be fully inactivated by prepulses to –50 mV and was partially amiloride sensitive. Recordings from newly generated mutant flies demonstrated that DmαG (Ca(v)3 homolog) encoded the amiloride-sensitive portion of the transient LVA calcium current. We further demonstrated that the Ca(v)2 homolog, Dmca1A, mediated the amiloride-insensitive component of LVA current. This novel role of Ca(v)2 channels was substantiated by patch clamp recordings from conditional mutants, RNAi knock-downs, and following Dmca1A overexpression. In addition, we show that Dmca1A underlies the HVA somatodendritic calcium currents in vivo. Therefore, the Drosophila Ca(v)2 homolog, Dmca1A, underlies HVA and LVA somatodendritic calcium currents in the same neuron. Interestingly, DmαG is required for regulating LVA and HVA derived from Dmca1A in vivo. In summary, each vertebrate gene family for voltage-gated calcium channels is represented by a single gene in Drosophila, namely Dmca1D (Ca(v)1), Dmca1A (Ca(v)2) and DmαG (Ca(v)3), but the commonly held view that LVA calcium currents are usually mediated by Ca(v)3 rather than Ca(v)2 channels may require reconsideration.

Addresses

School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA. stefanie.ryglewski@asu.edu

Autoren

Stefanie Ryglewski
Kimberly Lance
Richard B Levine
Carsten Duch

DOI

10.1113/jphysiol.2011.222836

eISSN

1469-7793

Externe Identifier

PubMed Identifier: 22183725

Funding acknowledgements

NINDS NIH HHS: R01 NS057637

Open access

false

ISSN

0022-3751

Ausgabe der Veröffentlichung

4

Zeitschrift

The Journal of physiology

Schlüsselwörter

Motor Neurons
Animals
Drosophila
Calcium Channels
Drosophila Proteins
Models, Genetic

Sprache

eng

Medium

Print-Electronic

Online publication date

2011

Paginierung

809 - 825

Datum der Veröffentlichung

2012

Status

Published

Datum der Datenerfassung

2011

Titel

Ca(v)2 channels mediate low and high voltage-activated calcium currents in Drosophila motoneurons.

Sub types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Journal Article
Research Support, N.I.H., Extramural

Ausgabe der Zeitschrift

590

Datenquelle: Europe PubMed Central

Abstract

Different blends of membrane currents underlie distinct functions of neurons in the brain. A major step towards understanding neuronal function, therefore, is to identify the genes that encode different ionic currents. This study combined in situ patch clamp recordings of somatodendritic calcium currents in an identified adult Drosophila motoneuron with targeted genetic manipulation. Voltage clamp recordings revealed transient low voltage-activated (LVA) currents with activation between –60 mV and –70 mV as well as high voltage-activated (HVA) current with an activation voltage around –30 mV. LVA could be fully inactivated by prepulses to –50 mV and was partially amiloride sensitive. Recordings from newly generated mutant flies demonstrated that DmαG (Ca(v)3 homolog) encoded the amiloride-sensitive portion of the transient LVA calcium current. We further demonstrated that the Ca(v)2 homolog, Dmca1A, mediated the amiloride-insensitive component of LVA current. This novel role of Ca(v)2 channels was substantiated by patch clamp recordings from conditional mutants, RNAi knock-downs, and following Dmca1A overexpression. In addition, we show that Dmca1A underlies the HVA somatodendritic calcium currents in vivo. Therefore, the Drosophila Ca(v)2 homolog, Dmca1A, underlies HVA and LVA somatodendritic calcium currents in the same neuron. Interestingly, DmαG is required for regulating LVA and HVA derived from Dmca1A in vivo. In summary, each vertebrate gene family for voltage-gated calcium channels is represented by a single gene in Drosophila, namely Dmca1D (Ca(v)1), Dmca1A (Ca(v)2) and DmαG (Ca(v)3), but the commonly held view that LVA calcium currents are usually mediated by Ca(v)3 rather than Ca(v)2 channels may require reconsideration.

Autoren

Stefanie Ryglewski
Kimberly Lance
Richard B Levine
Carsten Duch

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/22183725

DOI

10.1113/jphysiol.2011.222836

eISSN

1469-7793

Externe Identifier

PubMed Central ID: PMC3381312

Funding acknowledgements

NINDS NIH HHS: R01 NS057637

Ausgabe der Veröffentlichung

4

Zeitschrift

J Physiol

Schlüsselwörter

Animals
Calcium Channels
Drosophila
Drosophila Proteins
Models, Genetic
Motor Neurons

Sprache

eng

Country

England

Paginierung

809 - 825

PII

jphysiol.2011.222836

Datum der Veröffentlichung

2012

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2012

Titel

Ca(v)2 channels mediate low and high voltage-activated calcium currents in Drosophila motoneurons.

Sub types

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Ausgabe der Zeitschrift

590

Datenquelle: PubMed

Cav2 channels mediate low and high voltage-activated calcium currents in Drosophila motoneurons

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