High-voltage-activated calcium channels in Muller cells acutely isolated from tiger salamander retina

Glia. 2005 Jan 15;49(2):259-74. doi: 10.1002/glia.20113.

Abstract

Muller cells mediate retinal function by stabilizing the ionic environment and signal glial network activity via calcium waves. Using whole-cell patch clamp recording, we describe a high-voltage-activated, slowly inactivating Ca channel current in isolated salamander Muller cells that has unusual pharmacological properties. The Ca channel current has an activation midpoint of approximately -8 mV and an inactivation midpoint of approximately -26 mV in 10 mM Ba2+. The time constant for inactivation is approximately 380 ms at potentials positive to zero. The current is blocked by Cd2+ with an EC50 of <100 nM. nisoldipine (10 microM) blocks approximately 50%, while nifedipine (1 microM), diltiazem (20 microM), and verapamil (50 microM) each block one-third of the current. In contrast to its typical actions, BayK 8644 blocks the current by approximately 25%. Blockers of other Ca channel subtypes were also tested: omega-agatoxin IVA (200 nM) blocked only 13% of the Ca channel current, while omega-conotoxin GVIA (1 microM) blocked 84% of the current. Immnohistochemistry supported the presence of alpha1A, alpha1B, alpha1C, and alpha1D Ca channel subunits. Mapping of dihydropyridine-binding sites with DM-BODIPY revealed a distribution of channels over the entire membrane of the Muller cell with a higher density at the apical region. Overall, these observations suggest either the presence of a mix of L- and N-type Ca channels or a single, unconventional HVA Ca channel subtype sharing L- and N-type Ca channel characteristics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ambystoma
  • Animals
  • Binding Sites / drug effects
  • Binding Sites / physiology
  • Boron Compounds
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / physiology*
  • Calcium Channels, L-Type / drug effects
  • Calcium Channels, L-Type / physiology
  • Calcium Channels, N-Type / drug effects
  • Calcium Channels, N-Type / physiology
  • Cell Membrane / metabolism
  • In Vitro Techniques
  • Larva
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neuroglia / drug effects
  • Neuroglia / physiology*
  • Neurotoxins / pharmacology
  • Patch-Clamp Techniques
  • Protein Subunits / drug effects
  • Protein Subunits / metabolism
  • Receptor Aggregation / physiology
  • Retina / drug effects
  • Retina / physiology*

Substances

  • 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
  • Boron Compounds
  • Calcium Channel Blockers
  • Calcium Channels
  • Calcium Channels, L-Type
  • Calcium Channels, N-Type
  • Neurotoxins
  • Protein Subunits