High‐voltage‐activated calcium channels in Müller cells acutely isolated from tiger salamander retina

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.

Comparative electrophysiology of retinal Müller glial cells—A survey on vertebrate species

“…In the experiments described in Fig. , the solutions used by Bringmann et al (), Newman (), and Welch et al () to block K + currents completely were not applied. This might be the reason why voltage‐dependent Ca 2+ currents were not activated.…”

“…He demonstrated the presence of a voltage‐dependent Ca 2+ channel, a Ca 2+ ‐activated K + channel, and a fast inactivating (A‐type) K + channel. Currents through Ca 2+ channels in Müller cells were also recorded by Welch et al () in Ambystoma tigrinum and by Bringmann et al () in Bufo marinus . Total blocking of K + currents might be a precondition for experimental activation of Ca 2+ channels.…”

Association of Whirlin with Cav1.3 (α1D) Channels in Photoreceptors, Defining a Novel Member of the Usher Protein Network

“…35 In the salamander retina, immunoreactivity is observed in the GCL, Müller cells, the IPL, the OPL, and the photoreceptor inner segment. 36,37 During development, the murine Cacna1d gene is widely expressed (e.g., in the eye, the inner ear, and the CNS). Of note, Whrn expression has also been detected in these tissues.…”

Decreases in Pheromonal Responses at the Accessory Olfactory Bulb of Mice with a Deficiency of the .ALPHA.1B or .BETA.3 Subunits of Voltage-Dependent Ca2+-Channels

“…In the vomeronasal sensory epithelium, not only sensory neurons but also supporting cells, i.e., glial cells, have a 1B subunits. It has been reported that glial cells, such as astrocytes 27) and muller cells, 28) channels, however, are not normally involved in excitatory transmitter release. 8) However, there have been no electrophysiological studies indicating the existence of N-type and/or P/Q type Ca 2ϩ channels that play a role as key molecules in the neurotransmitter release between VSN and mitral/tufted cells in the AOB.…”