Intrinsically photosensitive retinal ganglion cells (ipRGCs) signal not only anterogradely to drive behavioral responses, but also retrogradely to some amacrine interneurons to modulate retinal physiology. We previously found that all displaced amacrine cells with spiking, tonic excitatory photoresponses receive gap-junction input from ipRGCs, but the connectivity patterns and functional roles of ipRGC-amacrine coupling remained largely unknown. Here, we injected PoPro1 fluorescent tracer into all six types of mouse ipRGCs to identify coupled amacrine cells, and analyzed the latter’s morphological and electrophysiological properties. We also examined how genetically disrupting ipRGC-amacrine coupling affected ipRGC photoresponses. Results showed that ipRGCs couple with not just ON- and ON/OFF-stratified amacrine cells in the ganglion-cell layer as previously reported, but also OFF-stratified amacrine cells in both ganglion-cell and inner nuclear layers. M1- and M3-type ipRGCs couple mainly with ON/OFF-stratified amacrine cells, whereas the other ipRGC types couple almost exclusively with ON-stratified ones. ipRGCs transmit melanopsin-based light responses to at least 93% of the coupled amacrine cells. Some of the ON-stratifying ipRGC-coupled amacrine cells exhibit transient hyperpolarizing light responses. We detected bidirectional electrical transmission between an ipRGC and a coupled amacrine cell, although transmission was asymmetric for this particular cell pair, favoring the ipRGC-to-amacrine direction. We also observed electrical transmission between two amacrine cells coupled to the same ipRGC. In both scenarios of coupling, the coupled cells often spiked synchronously. While ipRGC-amacrine coupling somewhat reduces the peak firing rates of ipRGCs’ intrinsic melanopsin-based photoresponses, it renders these responses more sustained and longer-lasting. In summary, ipRGCs’ gap junctional network involves more amacrine cell types and plays more roles than previously appreciated.

A hypothesis is proposed about potassium ponds being the cradles of life enriches the gamut of ideas about the possible conditions of pre-biological evolution on the primeval Earth, but does not bring us closer to solving the real problem of the origin of life. The gist of the matter lies in the mechanism of making a delimitation between two environments – the intracellular environment and the habitat of protocells. Since the sodium–potassium pump (Na+/K+-ATPase) was discovered, no molecular model has been proposed for a predecessor of the modern sodium pump. This has brought into life the idea of the potassium pond, wherein protocells would not need a sodium pump. However, current notions of the operation of living cells come into conflict with even physical laws when trying to use them to explain the origin and functioning of protocells. Thus, habitual explanations of the physical properties of living cells have become inapplicable to explain the corresponding properties of Sidney Fox's microspheres. Likewise, existing approaches to solving the problem of the origin of life do not see the need for the comparative study of living cells and cell models, assemblies of biological and artificial small molecules and macromolecules under physical conditions conducive to the origin of life. The time has come to conduct comprehensive research into the fundamental physical properties of protocells and create a new discipline – protocell physiology or protophysiology – which should bring us much closer to solving the problem of the origin of life.

Lithium is a potent psychotherapeutic agent that has gained wide acceptance in paediatrics, especially as adjunct treatment for severe behavioural, anxiety, and attention-deficit hyperactivity disorders, along with bipolar conditions. Its cardiac toxicity has been well-documented in adults; however, information is limited regarding lithium’s effects on the heart in children. Therefore, paediatric cardiologists following-up children on lithium therapy should be cognizant of the cardiac side-effects and pathophysiology associated with this drug. In this manuscript, we used an illustrative case of a child who presented with lithium poisoning, in order to highlight adverse clinical manifestations that can arise from this medication. The cardiac cell membrane is thought to be the primary site of lithium’s action. Thus, we reviewed lithium’s effects on membrane electrogenic pumps and channels involved in the distribution and passage of sodium, potassium, and calcium across the sarcolemma, as these ions, and their associated currents, are the primary determinates of the action potentials underlying auto-rhythmicity and contractile activity of the heart.

Little is known about the effects of undernutrition on the specific muscles and neuronal circuits involved in mastication. The aim of this study was to document the effects of neonatal low-protein diet on masticatory efficiency. Newborn rats whose mothers were fed 17 % (nourished (N), n 60) or 8 % (undernourished (U), n 56) protein were compared. Their weight was monitored and their masticatory jaw movements were video-recorded. Whole-cell patch-clamp recordings were performed in brainstem slice preparations to investigate the intrinsic membrane properties and N-methyl-d-aspartate-induced bursting characteristics of the rhythmogenic neurons (N, n 43; U, n 39) within the trigeminal main sensory nucleus (NVsnpr). Morphometric analysis (N, n 4; U, n 5) were conducted on masseteric muscles serial cross-sections. Our results showed that undernourished animals had lower numbers of masticatory sequences (P=0·049) and cycles (P=0·045) and slower chewing frequencies (P=0·004) (N, n 32; U, n 28). Undernutrition reduced body weight but had little effect on many basic NVsnpr neuronal electrophysiological parameters. It did, however, affect sag potentials (P<0·001) and rebound firing (P=0·005) that influence firing pattern. Undernutrition delayed the appearance of bursting and reduced the propensity to burst (P=0·002), as well as the bursting frequency (P=0·032). Undernourished animals showed increased and reduced proportions of fibre type IIA (P<0·0001) and IIB (P<0·0001), respectively. In addition, their fibre areas (IIA, P<0·001; IIB, P<0·001) and perimeters (IIA, P<0·001; IIB, P<0·001) were smaller. The changes observed at the behavioural, neuronal and muscular levels suggest that undernutrition reduces chewing efficiency by slowing, weakening and delaying maturation of the masticatory muscles and the associated neuronal circuitry.

Specialized conduction tissues mediate coordinated propagation of electrical activity through the adult vertebrate heart. Following activation of the atria, the activation wave is slowed down in the atrioventricular canal or node, after which it spreads rapidly into the left and right ventricles via the His-Purkinje system (HPS). This results in the ventricles being activated from the apex toward the base, which is a hallmark of HPS function. The development of mature HPS function follows significant phases of cardiac morphogenesis. Initially, the cardiac impulse propagates in a slow, linear, and isotropic fashion from the sinus venosus at the most caudal portion of the tubular heart. Although the speed of impulse propagation gradually increases as it travels toward the anterior regions of the heart tube, the actual sequence of ventricular activation in the looped heart proceeds in the same direction as blood flow. Eventually, the immature base-to-apex sequence of ventricular activation undergoes an apparent reversal, changing to the mature apex-to-base pattern. Using an optical mapping approach, we demonstrate that the timing of this last transition shows striking dependence on hemodynamic loading of the ventricle, being accelerated by pressure overload and delayed in left ventricular hypoplasia. Comparison of chick and mammalian hearts revealed some striking similarities as well as key differences in the timing of such events during cardiac organogenesis.

The intrinsic electrophysiological properties of medial geniculate body (MGB) neurons and their responses to noise bursts/pure tones were examined in the pentobarbital anesthetized guinea pig through intracellular recording. Discharge rate was calculated in the absence of acoustic stimuli over varied membrane potentials which were changed by intracellular injection of current or through automatic drifting. The non-acoustically-driven firing rate was 45.8 ± 23.3 Hz (mean ± S.D., n = 8) at membrane potentials of −45 mV, 30.6 ± 19.4 Hz (n = 14) at −50 mV, 18.0 ± 12.9 Hz (n = 14) at −55 mV, and significantly decreased to 5.7 ± 7.4 Hz at −60 mV, and to 0.7 ± 1.5 Hz (n = 10) at −65 mV (ANOVA, P < 0.001). The maximum non-acoustically-driven rate observed in the present study was 160 Hz. The auditory responsiveness of the MGB neurons was examined at membrane potentials over a range of −45 to −75 mV: the higher the membrane potential, the greater the responsiveness and vice versa. A putative non-low-threshold calcium spike (non-LTS) burst was observed in the present study. It showed significantly longer inter-spike intervals (11.6 ± 6.0 ms, P < 0.001, t-test) than those associated with the putative LTS bursts (6.7 ± 2.4 ms, P < 0.001, t-test). The dependence of the temporal structure of the spikes/spike bursts on the stimulus may provide insight into the temporal coding of sound information in the auditory system.

The voltage-gated calcium and sodium currents of starburst amacrine cells were examined in slices of the adult rabbit retina. ON-center starburst amacrine cells were targeted for whole-cell recording by prelabeling the retina with the nuclear dye 4′-6-diamidino-2-phenylindole hydrochloride (DAPI). Calcium currents were isolated using an external Ringer that contained tetrodotoxin to block sodium currents and barium to block potassium channels. When starburst amacrine cells were stepped to holding potentials positive to −50 mV, a series of voltage-dependent calcium currents were activated. The calcium current peaked at −10 mV. The calcium currents kinetics were mainly sustained in nature, showing only a small amount of slow inactivation. Nickel (100 μM), a T-type channel blocker, had no effect on the calcium current. Application of the L-type channel agonist BAY K8644 (1–2.5 μM) had small variable effects on the calcium current while the L-type channel antagonist nifedipine (10 μM) had no effect. However, addition of a reported N-type calcium channel antagonist, omega-conotoxin G6A (1 μM), blocked a large portion of the calcium current, as did a more nonselective antagonist, omega-conotoxin M7C (200 nM). Agatoxin 4A (500 nM) reduced a smaller sustained calcium current component, implying a P/Q-type calcium channel was present on these neurons. In addition to the calcium currents, a fast voltage-gated sodium current was observed in many starburst cells. This current could be blocked by tetrodotoxin (200–500 nM). The differing kinetics and durations of the sodium and calcium currents could play important roles in the regulation of synaptic release and in the coordination of spiking by starburst amacrine cell dendrites during retinal development and in the encoding of motion across the retinal surface.