Molecular elements of ion permeation and selectivity within calcium channels

Voltage-dependent calcium channels are located in the plasma membrane and form a highly selective conduit by which Ca2+ ions enter all excitable cells and some nonexcitable cells. Extensive characterization studies have revealed the existence of one low (T) and five high-voltage-activated calcium channel types (L, N, P, Q, and R). The high voltage-activated calcium channels have been found to exist as heteromultimers, consisting of an alpha(1), beta, alpha(2)/delta, and gamma subunit. Molecular cloning has revealed the existence of 10 channel transcripts, and expression of these cloned calcium channel genes has shown that basic voltage-activated calcium channel function is strictly carried by the corresponding a, subunits. In turn, the auxiliary subunits serve to modulate calcium channel function by altering the voltage dependence of channel gating, kinetics, and current amplitude, thereby creating a likelihood for calcium channels with multiple properties. Although for calcium channels to be effective, Ca2+ ions must enter selectively through the pore of the alpha(1)-subunit, bypassing competition with other extracellular ions. The structural determinants of this highly selective Ca2+ filter reside within the four glutamic acid residues located at homologous positions within each of the four pore-forming segments. Together, these residues form a single or multiple Ca2+ affinity site(s) that entrap calcium ions, which are then electrostatically repulsed through the intracellular opening of the pore. This mechanism of high-selectivity calcium filtration, the spatial arrangement of pore glutamic acid residues; and the coordination chemistry of calcium binding are discussed in this review

North American montane red foxes: expansion, fragmentation, and the origin of the Sacramento Valley red fox

Most native red foxes (Vulpes vulpes) in the western contiguous United States appear to be climatically restricted to colder regions in the major mountain ranges and, in some areas, have suffered precipitous declines in abundance that may be linked to warming trends. However, another population of unknown origin has occurred in arid habitats in the Sacramento Valley of California well outside this narrow bioclimatic niche since at least 1880. If native, this population would be ecologically distinct among indigenous North American red foxes. We used mitochondrial and microsatellite markers from historical and modern samples (modes: 1910–1930 and 2000–2008, respectively) obtained throughout the western United States to determine the origins of the Sacramento Valley red fox, and assess the historical and modern connectivity and genetic effective population sizes of Sacramento Valley and montane red foxes. We found clear and consistent evidence supporting the indigenous origin of the Sacramento Valley population, including the phylogenetic positioning of the dominant, endemic mtDNA clade and microsatellite clustering of the Sacramento Valley population with the nearest montane population. Based on both mitochondrial and microsatellite AMOVAs, connectivity among Western populations of red foxes declined substantially between historical and modern time periods. Estimates based on temporal losses in gene diversity for both marker types suggest that both the Sierra Nevada (including the Southern Cascades population) and the Sacramento Valley populations have small genetic effective population sizes. Significant heterozygote excesses also indicate the occurrence of recent bottlenecks in these populations. Both substitutions distinguishing the 2 endemic Sacramento Valley haplotypes from the dominant montane haplotype were in the coding region and nonsynonymous, consistent with adaptive differences. These findings along with previously reported body size distinctions between Sacramento Valley and montane red foxes argue for distinct subspecific status for the Sacramento Valley red fox, for which we propose the designation V. v. patwin n. subsp. The small genetic effective population size estimates for the Sierra Nevada red fox and Sacramento Valley red fox are cause for concern, as is the possibility of genetic introgression into the latter population from an adjacent, recently established nonnative population