Developmental Regulation of Calcium Channel-Mediated Currents in Retinal Glial (Müller) Cells

Abstract

Whole cell voltage-clamp recordings of freshly isolated cells were used to study changes in the currents through voltage-gated Ca(2+) channels during the postnatal development of immature radial glial cells into Müller cells of the rabbit retina. Using Ba(2+) or Ca(2+) ions as charge carriers, currents through transient low-voltage-activated (LVA) Ca(2+) channels were recorded in cells from early postnatal stages, with an activation threshold at -60 mV and a peak current at -25 mV. To increase the amplitude of currents through Ca(2+) channels, Na(+) ions were used as the main charge carriers, and currents were recorded in divalent cation-free bath solutions. Currents through transient LVA Ca(2+) channels were found in all radial glial cells from retinae between postnatal days 2 and 37. The currents activated at potentials positive to -80 mV and displayed a maximum at -40 mV. The amplitude of LVA currents increased during the first postnatal week; after postnatal day 6, the amplitude remained virtually constant. The density of LVA currents was highest at early postnatal days (days 2-5: 13 pA/pF) and decreased to a stable, moderate level within the first three postnatal weeks (3 pA/pF). A significant expression of currents through sustained, high-voltage-activated Ca(2+) channels was found after the third postnatal week in approximately 25% of the investigated cells. The early and sole expression of transient currents at high-density may suggest that LVA Ca(2+) channels are involved in early developmental processes of rabbit Müller cells.

Ion Channel Development, Spontaneous Activity, and Activity-Dependent Development in Nerve and Muscle Cells

“…The impact of a current on firing properties is more closely related to its density, and as cells grow during development, it is important to know whether changes in current amplitude keep pace with, fall short of, or exceed the amount of membrane added. A similar finding was made for the T-type Ca 2ϩ current in Muller glial cells: current amplitude held constant during early postnatal development, but because there was extensive cell growth, current density fell substantially (75). Although current amplitude and capacitance (a measure of surface area) are not always measured over the same compartments because they are measured at different frequencies, at least an approximate indication of true current density should be monitored along with current magnitude in developmental studies where cell size and/or shape are changing.…”

“…Reduction in T-type currents occurs during the early development of spinal neurons (213,380,387), embryonic skeletal muscle (26,39,204), cardiac myocytes (172,217,327), Muller glial cells (75), cortical and hippocampal neurons (94,584), vestibular neurons (93), neu-ronal cell lines (310,314), chromaffin cells (70), and others. In cardiac and skeletal muscle, the T-type currents that are downregulated are of the ␣ 1G and ␣ 1H types (39,172,327).…”

Molecular Identity and Functional Properties of a Novel T-Type Ca2+ Channel Cloned From the Sensory Epithelia of the Mouse Inner Ear

“…Also important, the robust expression of Ca v 3.1 and reappearance in regenerating hair cells is in further agreement with the concept that expression of T-type currents begets cellular development. T-type currents are frequently observed in the early development of cells and their density, amplitude, and properties change over time as seen in embryonic dorsal root ganglia, retinal Müller cells, hippocampal neurons, and thalamocortical cells (Bringmann et al 2000;Desmadryl et al 1998;Pirchio et al 1990;Yaari et al 1987). Moreover, in some cell types, T-type current density decreases with age until a mature stage is reached.…”

Potassium attenuates zinc‐induced death of cultured cortical astrocytes

“…The presence of 400 M Zn 2ϩ reduced the resting potential in our glial cultures from Ϫ68.6 Ϯ 2.7 mV to Ϫ55.8 Ϯ 3.2 mV (n ϭ 18, P Ͻ 0.01). Such depolarization is sufficient to induce activation of the low voltage activated T-type Ca 2ϩ channel (Bringmann et al, 2000) or channels from the cloned ␣ 1G subunit (Monteil et al, 2000). …”