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The mitochondrial calcium uniporter is a highly selective channel responsible for mitochondrial Ca(2+) uptake. The mitochondrial calcium uniporter shapes cytosolic Ca(2+) signals, controls mitochondrial ATP production, and is involved in cell death. Here using direct patch-clamp recording from the inner mitochondrial membrane, we compare mitochondrial calcium uniporter activity in mouse heart, skeletal muscle, liver, kidney and brown fat. Surprisingly, heart mitochondria show a dramatically lower mitochondrial calcium uniporter current density than the other tissues studied. Similarly, in Drosophila flight muscle, mitochondrial calcium uniporter activity is barely detectable compared with that in other fly tissues. As mitochondria occupy up to 40% of the cell volume in highly metabolically active heart and flight muscle, low mitochondrial calcium uniporter activity is likely essential to avoid cytosolic Ca(2+) sink due to excessive mitochondrial Ca(2+) uptake. Simultaneously, low mitochondrial calcium uniporter activity may also prevent mitochondrial Ca(2+) overload in such active tissues exposed to frequent cytosolic Ca(2+) activity.

Somatostatin (somatotropin release-inhibiting factor, SRIF) receptor subtypes are expressed by several retinal neurons, suggesting that SRIF acts at multiple levels of the retinal circuitry, although functional data on this issue are scarce. Of the SRIF receptors, the sst2A isoform is expressed by rod bipolar cells (RBCs) of the rabbit retina, and in isolated RBCs we studied the role of sst2 receptors in modulating both K+ current (IK) and the intracellular free [Ca2+] ([Ca2+]i) using both voltage-clamp and Ca2+-imaging techniques. SRIF and octreotide (a SRIF agonist that binds to sst2 receptors) inhibited that component of IK corresponding to the activation of large-conductance, Ca2+- and voltage-dependent K+ channels (IBK) and reduced the K+-induced [Ca2+]i accumulation, suggesting that SRIF effects on IBK may have been secondary to inhibition of Ca2+ channels. Octreotide effects on IBK or on [Ca2+]i accumulation were prevented by RBC treatment with L-Tyr8-Cyanamid 154806, a novel sst2 receptor antagonist, indicating that SRIF effects were mediated by sst2 receptor activation. The present data indicate that SRIF may modulate the information flow through second-order retinal neurons via an action predominantly at sst2 receptors, contribute to the proposition that SRIF be added to the growing list of retinal neuromodulators, and suggest that one of its possible roles in the retina is to regulate transmitter release from RBCs. [ABSTRACT FROM AUTHOR]

Arising from M. A. Joiner et al. 491, 269-273 (2012); doi:10.1038/nature10234The influx of cytosolic Ca2+ into mitochondria is mediated primarily by the mitochondrial calcium uniporter (MCU), a small-conductance, Ca2+-selective channel-MCU modulates intracellular Ca2+ transients and regulates ATP production and cell death. Recently, Joiner et al. reported that MCU is regulated by mitochondrial CaMKII, and this regulation determines stress response in heart. They reported a very large current putatively mediated by MCU that was about two orders of magnitude greater than the MCU current (IMCU) that we previously measured in heart mitochondria; furthermore, the current traces presented by Joiner et al. showed unusually high fluctuations incompatible with the low single-channel conductance of MCU. Here we performed patch-clamp recordings from mouse heart mitochondria under the exact conditions used by Joiner et al., and confirm that IMCU in cardiomyocytes is very small and is not directly regulated by CaMKII; thus, the currents presented by Joiner et al. do not appear to correspond to MCU, and there is no direct electrophysiological evidence that CaMKII regulates MCU. There is a Reply to this Brief Communication Arising by Joiner, M. A. et al. Nature 513, http://dx.doi.org/10.1038/nature13627 (2014). [ABSTRACT FROM AUTHOR]

The mammalian vomeronasal organ (VNO) contains specialized neurones that transduce the chemical information related to pheromones into discharge of action potentials to the brain. Molecular and biochemical studies have shown that specific components of the pheromonal transduction systems are segregated into two distinct subsets of vomeronasal neurones: apical neurones and basal neurones. However, it is still unknown whether these neuronal subsets also differ in other functional characteristics, such as their membrane properties. We addressed this issue by studying the electrophysiological properties of vomeronasal neurones isolated from mouse VNO. We used the patch-clamp technique to examine both the passive membrane properties and the voltage-gated Na+, K+ and Ca2+ currents. Apical neurones were distinguished from basal ones by the length of their dendrites and by their distinct immunoreactivity for the putative pheromone receptor V2R2. The analysis of passive properties revealed that there were no significant differences between the two neuronal subsets. Also, apical neurones were similar to basal neurones in their biophysical and pharmacological properties of voltage-gated Na+ and K+ currents. However, we found that the density of Na+ currents was about 2-3 times greater in apical neurones than in basal neurones. Consistently, in situ hybridization analysis revealed a higher expression of the Na+ channel subtype III in apical neurones than in basal ones. In contrast, basal neurones were endowed with Ca2+ currents (T-type) of greater magnitude than apical neurones. Our findings indicate that apical and basal neurones in the VNO exhibit distinct electrical properties. This might have a profound effect on the sensory processes occurring in the VNO during pheromone detection.