Mechanism of Generation of Spontaneous Miniature Outward Currents (SMOCs) in Retinal Amacrine Cells

Abstract

A subtype of retinal amacrine cells displayed a distinctive array of K+ currents. Spontaneous miniature outward currents (SMOCs) were observed in the narrow voltage range of −60 to −40 mV. Depolarizations above approximately −40 mV were associated with the disappearance of SMOCs and the appearance of transient (Ito) and sustained (Iso) outward K+ currents. Ito appeared at about −40 mV and its apparent magnitude was biphasic with voltage, whereas Iso appeared near −30 mV and increased linearly. SMOCs, Ito, and a component of Iso were Ca2+ dependent. SMOCs were spike shaped, occurred randomly, and had decay times appreciably longer than the time to peak. In the presence of cadmium or cobalt, SMOCs with pharmacologic properties identical to those seen in normal Ringer's could be generated at voltages of −20 mV and above. Their mean amplitude was Nernstian with respect to [K+]ext and they were blocked by tetraethylammonium. SMOCs were inhibited by iberiotoxin, were insensitive to apamin, and eliminated by nominally Ca2+-free solutions, indicative of BK-type Ca2+-activated K+ currents. Dihydropyridine Ca2+ channel antagonists and agonists decreased and increased SMOC frequencies, respectively. Ca2+ permeation through the kainic acid receptor had no effect. Blockade of organelle Ca2+ channels by ryanodine, or intracellular Ca2+ store depletion with caffeine, eradicated SMOCs. Internal Ca2+ chelation with 10 mM BAPTA eliminated SMOCs, whereas 10 mM EGTA had no effect. These results suggest a mechanism whereby Ca2+ influx through L-type Ca2+ channels and its subsequent amplification by Ca2+-induced Ca2+ release via the ryanodine receptor leads to a localized elevation of internal Ca2+. This amplified Ca2+ signal in turn activates BK channels in a discontinuous fashion, resulting in randomly occurring SMOCs.

Synaptic Transmission Mediated by Internal Calcium Stores in Rod Photoreceptors

“…Presumably, stochastic opening of a voltage-gated calcium channel allows calcium influx, leading to amplification of the calcium signal by ryanodine receptors, followed by vesicle fusion. A similar association of L-type calcium channels and ryanodine receptors produces stochastic activation of BK channels in amacrine cells (Mitra and Slaughter, 2002). Membrane calcium channels are clearly the initiators of mEPSCs because blocking Ca 2ϩ channels with cadmium completely eliminates them.…”

Serca isoform expression in the mammalian retina

“…SERCA2 is likely to represent the isoform responsible for refilling the ER through the periods of sustained low baseline [Ca 2+ ]i in light-adapted neurons. Ca 2+ release from intracellular stores and SERCA-mediated Ca 2+ sequestration are essential for sustaining intracellular Ca signaling during dendritic stratification (Lohmann et al, 2002), in control of membrane excitability (Mitra and Slaughter 2002;Hurtado et al, 2002), Ca 2+ homeostasis and synaptic signaling (Akopian and Witkovsky, 1996) of many classes of retinal neuron. Moreover, SERCA2 is likely to regulate Ca 2+ signaling that underlies the developmental and functional plasticity of retinal networks, as documented in many types of central neurons (Harvey and Collingridge, 1992;Emptage et al, 2001;Cong et al, 2004).…”

“…The functional roles of Ca 2+ stores in retinal neurons include control of development, membrane excitability, AMPA and GABA receptor function and synaptic transmission (Krizaj et al, 1999;Hurtado et al, 2002;Mitra and Slaughter, 2002;Witkovsky, 1998, 2001). It is likely that Ca 2+ release/sequestration play an essential role in the development, signaling and apoptosis of retinal neurons in mammals and birds (Lohmann et al, 2002).…”

The Role of BKCa Channels in Electrical Signal Encoding in the Mammalian Auditory Periphery

“…In nonmammalian auditory hair cells, BK Ca contributes to electrical frequency tuning in the absence of APs (Art and Fettiplace, 1987;Fettiplace and Fuchs, 1999). However, less is known about the impact of BK Ca on electrical signaling in other nonspiking cells, such as retinal neurons (Sakaba et al, 1997;Mitra and Slaughter, 2002) or mechanosensory hair cells of the mammalian ear, despite strong expression of BK Ca in these cells (Skinner et al, 2003;Vigh et al, 2003). Mammalian inner hair cells (IHCs) are a useful system to study the role of BK Ca in nonregenerative electrical signaling operating in a frequency range far beyond that of usual neurons.…”