Plasma membrane Ca 2؉-ATPase isoform 2 (PMCA2) exhibits a highly restricted tissue distribution, suggesting that it serves more specialized physiological functions than some of the other isoforms. A unique role in hearing is indicated by the high levels of PMCA2 expression in cochlear outer hair cells and spiral ganglion cells. To analyze the physiological role of PMCA2 we used gene targeting to produce PMCA2-deficient mice. Breeding of heterozygous mice yielded live homozygous mutant offspring. PMCA2-null mice grow more slowly than heterozygous and wild-type mice and exhibit an unsteady gait and difficulties in maintaining balance. Histological analysis of the cerebellum and inner ear of mutant and wild-type mice revealed that null mutants had slightly increased numbers of Purkinje neurons (in which PMCA2 is highly expressed), a decreased thickness of the molecular layer, an absence of otoconia in the vestibular system, and a range of abnormalities of the organ of Corti. Analysis of auditory evoked brainstem responses revealed that homozygous mutants were deaf and that heterozygous mice had a significant hearing loss. These data demonstrate that PMCA2 is required for both balance and hearing and suggest that it may be a major source of the calcium used in the formation and maintenance of otoconia.Calmodulin-dependent plasma membrane Ca 2ϩ -ATPases (PMCAs) 1 are highly regulated enzymes that maintain the appropriate concentrations of intracellular free Ca 2ϩ by extruding Ca 2ϩ from the cell (1, 2). There are four mammalian PMCA isoforms (PMCA1-4), each encoded by a distinct gene (3-8), and additional diversity is generated by alternative splicing of exons encoding the regulatory domains (7, 9 -11). Variants of PMCA1 and PMCA4 are expressed in many different tissues and cell types, whereas variants of PMCA2 and PMCA3 exhibit a highly restricted distribution (5,8,12). This suggests that specific isoforms and splice variants serve different physiological functions. However, despite extensive information about PMCA structural diversity, expression patterns, and biochemical and regulatory characteristics, little is known about the functions of individual isoforms in vivo.Its unique biochemical characteristics (13, 14) and tissue specificity (5, 10 -12) suggest that PMCA2 might serve specialized physiological functions. In situ hybridization studies revealed that expression of PMCA2 is particularly high in Purkinje neurons of the cerebellum (15) and in the spiral ganglion nerves of the inner ear and outer hair cells of the cochlea (16). The observation that PMCA2 is the predominant isoform in outer hair cells (16) suggests that it might be the isoform that is expressed at high levels in stereocilia (17), which comprise hair bundles, the sensory organelles that mediate mechanoelectrical transduction by hair cells of both the vestibular and auditory systems (18,19). A recent study demonstrated that PMCA activity in the stereocilia of vestibular hair cells regulates hair bundle Ca 2ϩ concentrations and indicated that it ...

No abstract

It is known that plasma membrane Ca(2+)-transporting ATPases (PMCAs) extrude Ca(2+) from the cell and that sarco(endo)plasmic reticulum Ca(2+)-ATPases (SERCAs) and secretory pathway Ca(2+)-ATPases (SPCAs) sequester Ca(2+) in intracellular organelles; however, the specific physiological functions of individual isoforms are less well understood. This information is beginning to emerge from studies of mice and humans carrying null mutations in the corresponding genes. Mice with targeted or spontaneous mutations in plasma membrane Ca(2+)-ATPase isoform 2 (PMCA2) are profoundly deaf and have a balance defect due to the loss of PMCA2 in sensory hair cells of the inner ear. In humans, mutations in SERCA1 (ATP2A1) cause Brody disease, an impairment of skeletal muscle relaxation; loss of one copy of the SERCA2 (ATP2A2) gene causes Darier disease, a skin disorder; and loss of one copy of the SPCA1 (ATP2C1) gene causes Hailey-Hailey disease, another skin disorder. In the mouse, SERCA2 null mutants do not survive to birth, and heterozygous SERCA2 mutants have impaired cardiac performance and a high incidence of squamous cell cancers. SERCA3 null mutants survive and appear healthy, but endothelium-dependent relaxation of vascular smooth muscle is impaired and Ca(2+) signaling is altered in pancreatic beta cells. The diversity of phenotypes indicates that the various Ca(2+)-transporting ATPase isoforms serve very different physiological functions.

The decomposition of diversity into within site (α) and between site (β) components is especially interesting in subterranean communities because of their isolated nature and limited dispersal potential The aquatic epikarst fauna, sampled from water drips in caves affords a unique opportunity to provide comparable, quantitative samples of a portion of the obligate subterranean dwelling fauna in multiple hierarchical levels. We focused on three interrelated questions—(1) what is the spatial pattern of epikarst species diversity; (2) how does species diversity partition between local, and regional components (nested and replacement); and (3) whether epikarst hotspots are subterranean hotspots in general. We analyzed the geographic pattern of species richness of 30 species of obligate subterranean copepods found in 81 drips in Slovenian caves in three karst regions—Alpine, Dinaric, and Isolated. Comparison of Chao1 and observed (Mao-tau) estimates of species richness indicated sampling in most drips was complete, but species accumulation curves indicated roughly half of the sites in the Dinaric karst had not reached an asymptote. Overall, within drip diversity accounted for three species, different drips in a cave another three, different caves in a region six species, and different regions accounted for the remaining 18 species. Sites in the Dinaric karst had much higher species richness than the other sites, which is in agreement with studies of other components of the subterranean fauna. The fauna associated with drips in Županova jama (jama = cave), in the east-central Dinaric karst was the richest found. While turnover explained the majority of β-diversity, nestedness in the form of hotspot drips was important as well. A consequence is that a small number of drips largely determine cave and regional species diversity.

Troglobionts are organisms that are specialized for living in a subterranean environment. These organisms reside prevalently in the deepest zones of caves and in shallow subterranean habitats, and complete their entire life cycles therein. Because troglobionts in most caves depend on organic matter resources from the surface, we hypothesized that they would also select the sections of caves nearest the surface, as long as environmental conditions were favorable. Over 1 year, we analyzed, in monthly intervals, the annual distributional dynamics of a subterranean community consisting of 17 troglobiont species, in relation to multiple environmental factors. Cumulative standardized annual species richness and diversity clearly indicated the existence of two ecotones within the cave: between soil and shallow subterranean habitats, inhabited by soil and shallow troglobionts; and between the transition and inner cave zones, where the spatial niches of shallow and deep troglobionts overlap. The mean standardized annual species richness and diversity showed inverse relationships, but both contributed to a better insight into the dynamics of subterranean fauna. Regression analyses revealed that temperatures in the range 7–10°C, high moisture content of substrate, large cross section of the cave, and high pH of substrate were the most important ecological drivers governing the spatiotemporal dynamics of troglobionts. Overall, this study shows general trends in the annual distributional dynamics of troglobionts in shallow caves and reveals that the distribution patterns of troglobionts within subterranean habitats may be more complex than commonly assumed.