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Drosophila Voltage-Gated Calcium Channel α1-Subunits Regulate Cardiac Function in the Aging Heart

Alexander Lam1, Priyanka Karekar1, Kajol Shah1

  • 1Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, 19102, USA.

Scientific Reports
|May 4, 2018
PubMed

Insights

Voltage-gated calcium channels (VGCCs) regulate reactive oxygen species (ROS) stress and lifespan in fruit flies. Specific VGCC subtypes show distinct roles in ROS handling, lifespan, and age-dependent cardiac function.

Area of Science:

  • Physiology
  • Molecular Biology
  • Genetics

Background:

  • Ion channels are crucial for physiological functions and cellular signaling.
  • Reactive oxygen species (ROS) interact with ion channels, influencing cellular homeostasis.
  • Voltage-gated calcium channels (VGCCs) are key regulators of cellular signaling and function.

Purpose of the Study:

  • To identify ion channels involved in reactive oxygen species (ROS) handling and survival using a paraquat (PQ) screen in Drosophila.
  • To investigate the specific roles of different α1-subunits of VGCCs in response to ROS stress.
  • To determine the impact of VGCCs on lifespan and cardiac function in an age-dependent manner.

Main Methods:

  • Paraquat (PQ) screening in Drosophila melanogaster to identify genes affecting ROS stress.
  • Genetic manipulation of α1-subunits (D-type, T-type, cacophony) of VGCCs.
  • Lifespan assays to assess the effect of VGCCs on longevity.
  • Optical coherence tomography (OCT) to evaluate cardiac function in aging fruit flies.

Main Results:

  • The screen identified α1-subunits of VGCCs (D-type, T-type, cacophony) as regulators of PQ-mediated ROS stress, with differential effects based on gender.
  • Absence of T-type and cacophony VGCCs decreased lifespan, while D-type VGCCs did not alter lifespan compared to wild-type.
  • OCT analysis revealed that VGCC α1-subunits are essential for maintaining cardiac rhythmicity and function, particularly in aging flies.

Conclusions:

  • Specific α1-subunits of VGCCs play distinct roles in managing ROS stress and influencing lifespan in Drosophila.
  • VGCCs are critical for maintaining cardiac function throughout aging.
  • These findings highlight the intricate relationship between ion channels, ROS signaling, and age-related physiological decline.

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