A note on the evolution of the transducer mechanism of the vertebrate retinal rod

Summary The Ca²⁺-gating mechanism that is the key component of membrane excitability in Paramecium has recently been localized on the cilia of this animal. Such a finding shows how the change in Ca²⁺ permeability (which is the probable consequence of the photoisomerization of rhodopsin) of the discs of the outer segments of the retinal rods could have evolved.     

An SCN9A channelopathy causes congenital inability to experience pain

The complete inability to sense pain in an otherwise healthy individual is a very rare phenotype. In three consanguineous families from northern Pakistan, we mapped the condition as an autosomal-recessive trait to chromosome 2q24.3. This region contains the gene SCN9A, encoding the alpha-subunit of the voltage-gated sodium channel, Na(v)1.7, which is strongly expressed in nociceptive neurons. Sequence analysis of SCN9A in affected individuals revealed three distinct homozygous nonsense mutations (S459X, I767X and W897X). We show that these mutations cause loss of function of Na(v)1.7 by co-expression of wild-type or mutant human Na(v)1.7 with sodium channel beta(1) and beta(2) subunits in HEK293 cells. In cells expressing mutant Na(v)1.7, the currents were no greater than background. Our data suggest that SCN9A is an essential and non-redundant requirement for nociception in humans. These findings should stimulate the search for novel analgesics that selectively target this sodium channel subunit.     

Seismic waves increase permeability

Earthquakes have been observed to affect hydrological systems in a variety of ways--water well levels can change dramatically, streams can become fuller and spring discharges can increase at the time of earthquakes. Distant earthquakes may even increase the permeability in faults. Most of these hydrological observations can be explained by some form of permeability increase. Here we use the response of water well levels to solid Earth tides to measure permeability over a 20-year period. At the time of each of seven earthquakes in Southern California, we observe transient changes of up to 24 degrees in the phase of the water level response to the dilatational volumetric strain of the semidiurnal tidal components of wells at the Pi?on Flat Observatory in Southern California. After the earthquakes, the phase gradually returns to the background value at a rate of less than 0.1 degrees per day. We use a model of axisymmetric flow driven by an imposed head oscillation through a single, laterally extensive, confined, homogeneous and isotropic aquifer to relate the phase response to aquifer properties. We interpret the changes in phase response as due to changes in permeability. At the time of the earthquakes, the permeability at the site increases by a factor as high as three. The permeability increase depends roughly linearly on the amplitude of seismic-wave peak ground velocity in the range of 0.21-2.1 cm s(-1). Such permeability increases are of interest to hydrologists and oil reservoir engineers as they affect fluid flow and might determine long-term evolution of hydrological and oil-bearing systems. They may also be interesting to seismologists, as the resulting pore pressure changes can affect earthquakes by changing normal stresses on faults.     

A note on the mechanism of action of UV-irradiation of amphibian embryos

Summary The actions on amphibian embryos of UV-irradiation, exposure to Li⁺ or exposure to ouabain show interesting parallels with their effects on spontaneous release at the presynaptic terminals of the neuromuscular junction. It is suggested that these treatments serve to raise intracellular Ca²⁺ ([Ca²⁺ _i) in these examples, and that UV-promoted abnormalities in embryogenesis are a consequence of changes in [Ca²⁺]_i at critical stages in development.     

Human microphthalmia associated with mutations in the retinal homeobox gene CHX10

Isolated human microphthalmia/anophthalmia, a cause of congenital blindness, is a clinically and genetically heterogeneous developmental disorder characterized by a small eye and other ocular abnormalities. Three microphthalmia/anophthalmia loci have been identified, and two others have been inferred by the co-segregation of translocations with the phenotype. We previously found that mice with ocular retardation (the or-J allele), a microphthalmia phenotype, have a null mutation in the retinal homeobox gene Chx10 (refs 7,8). We report here the mapping of a human microphthalmia locus on chromosome 14q24.3, the cloning of CHX10 at this locus and the identification of recessive CHX10 mutations in two families with non-syndromic microphthalmia (MIM 251600), cataracts and severe abnormalities of the iris. In affected individuals, a highly conserved arginine residue in the DNA-recognition helix of the homeodomain is replaced by glutamine or proline (R200Q and R200P, respectively). Identification of the CHX10 consensus DNA-binding sequence (TAATTAGC) allowed us to demonstrate that both mutations severely disrupt CHX10 function. Human CHX10 is expressed in progenitor cells of the developing neuroretina and in the inner nuclear layer of the mature retina. The strong conservation in vertebrates of the CHX10 sequence, pattern of expression and loss-of-function phenotypes demonstrates the evolutionary importance of the genetic network through which this gene regulates eye development.