A Component of Calcium-activated Potassium Channels Encoded by the Drosophila slo Locus

Abstract

Calcium-activated potassium channels mediate many biologically important functions in electrically excitable cells. Despite recent progress in the molecular analysis of voltage-activated K+ channels, Ca(2+)-activated K+ channels have not been similarly characterized. The Drosophila slowpoke (slo) locus, mutations of which specifically abolish a Ca(2+)-activated K+ current in muscles and neurons, provides an opportunity for molecular characterization of these channels. Genomic and complementary DNA clones from the slo locus were isolated and sequenced. The polypeptide predicted by slo is similar to voltage-activated K+ channel polypeptides in discrete domains known to be essential for function. Thus, these results indicate that slo encodes a structural component of Ca(2+)-activated K+ channels.

Complementation of Physiological and Behavioral Defects by a Slowpoke Ca2+ ‐Activated K+ Channel Transgene

“…Genetic crosses were used to move the transgene into a homozygous slo 4 genetic background. The slo 4 mutations have been shown to eliminate the Ca 2ϩ -activated K ϩ current, I CF (Komatsu et al, 1990;Atkinson et al, 1991 …”

“…For our studies, the transgene was crossed into a slo 4 mutant background. We chose the slo 4 allele for all of our studies because the evidence that it is a null allele is very strong: first, this mutation is a chromosomal inversion with one end point near the 5Ј end of the gene; second, electrophysiological assays have shown a complete lack of I CF in flight muscle (Atkinson et al, 1991); and finally, neither in situ hybridization nor immunohistochemical staining with an antibody directed against the carboxy-terminal tail of the protein detected any expression products from the gene (Becker et al, 1995). Therefore, in the slo 4 background it is possible to replace the products of the endogenous gene with the product of the transgene.…”

“…The slowpoke gene encodes the channel that conducts the fast-activating, Ca 2ϩ -dependent current that in Drosophila is called I CF (Elkins et al, 1986;Atkinson et al, 1991). The Shaker gene produces the channel that conducts the fast-activating voltage-dependent current called I A (Baumann et al, 1987;Kamb et al, 1987;Papazian et al, 1987).…”

“…The channels that conduct these currents all appear to be products of the slowpoke gene. Channel diversity is thought to arise, in part, from alternative mRNA splicing and from the use of tissue-specific transcriptional promoters (Atkinson et al, 1991;Adelman et al, 1992;, both of which can alter the sequence of the encoded protein.…”

Modulation of the Ca2+-Activated Large Conductance K+ Channel by Intracellular pH in Human Renal Proximal Tubule Cells.

“…An elevation of cytoplasmic Ca 2ϩ concentration ([Ca 2ϩ ] i ) and depolarization of the membrane commonly stimulates activity of the BK channels [1][2][3]. It has already been proved by the use of cloned BK channels that the channel protein possesses the Ca 2ϩ -binding sites [4,5] and the voltagesensing domain [6,7]. Besides Ca 2ϩ and voltage, other factors such as ATP [8-11], pH [8, 9, 12-21], and Mg 2ϩ [19,[22][23][24] were also reported to modulate BK channels.…”