High impact information on slo

• Voltage-clamp analysis of Drosophila larval muscle revealed that ether à go-go (eag) mutations affected all identified potassium currents, including those specifically eliminated by mutations in the Shaker or slowpoke gene [1].
• A dynamically regulated 14-3-3, Slob, and Slowpoke potassium channel complex in Drosophila presynaptic nerve terminals [2].
• The open reading frames encode proteins ranging from 1154 to 1195 amino acids, and all possess significant identity with the slowpoke gene products in Drosophila and mouse [3].
• Calcium-activated potassium channels were expressed in Xenopus oocytes by injection of RNA transcribed in vitro from complementary DNAs derived from the slo locus of Drosophila melanogaster [4].
• In the present study, we have taken advantage of flies exhibiting a distinctive arrhythmic phenotype due to mutation of the potassium channel slowpoke (slo) to examine the relevance of specific neuronal populations involved in the circadian control of behavior [5].

Biological context of slo

• A mutation that eliminates slo expression prevents tolerance, whereas expression from an inducible slo transgene mimics tolerance in naive animals [6].
• It is the sedative phase that stimulates slo gene expression and induces tolerance [6].
• slo K(+) channel gene regulation mediates rapid drug tolerance [6].
• During pupariation and embryogenesis, slo is expressed in muscles many hours prior to the appearance of functional channels [7].
• BK channel activity underlies the fast afterhyperpolarization that follows an action potential and attenuates neurotransmitter and hormone secretion [8].

Anatomical context of slo

• Fura-2-based imaging revealed in cultured embryonic neurons that the loss of either voltage-gated, inactivating Shaker channels or Ca(2+)-gated Slowpoke BK channels led to robust spontaneous Ca(2+) transients that preferentially occurred within the growth cone [9].
• Interestingly, loss of Slowpoke currents strongly influenced tubulin regulation, enhancing the number of microtubule loop structures per growth cone [9].
• Here we describe the effects of mutations in the slowpoke gene, which is the structural gene for a calcium activated potassium channel, on transmitter release at the neuromuscular junction in Drosophila melanogaster [10].
• To date, five transcriptional promoters have been identified, which are responsible for slowpoke expression in neurons, midgut cells, tracheal cells, and muscle fibers [11].
• Unlike native BK channels from rat skeletal muscle in which increasing internal Ca2+ concentration (Cai2+) in the range of 5 to 30 microM increases mean open time, increasing Cai2+ in this range for dSlo had little effect on mean open time [12].

Associations of slo with chemical compounds

• We used Sh, slo and quinidine to remove specifically one or more K+ currents, so as to study physiological properties of these currents not previously characterized, and to examine their role in membrane excitability [13].
• In Drosophila, a single sedation with the anesthetic benzyl alcohol changes the expression of the slo K(+) channel gene and induces rapid drug tolerance [6].
• Mechanisms of Two Modulatory Actions of the Channel-binding Protein Slob on the Drosophila Slowpoke Calcium-dependent Potassium Channel [14].
• The slowpoke gene is necessary for rapid ethanol tolerance in Drosophila [15].
• Furthermore, the slowpoke mutation suppresses the striking increase in transmitter release that occurs following application of 4-aminopyridine to the ether a go-go mutant [10].

Physical interactions of slo

• Direct application of Slob to the cytoplasmic face of detached membrane patches containing dSlo channels leads to an increase in channel activity [16].
• Furthermore, the catalytically inactive PKAc mutant does bind to dSlo but does not modulate channel activity [17].

Regulatory relationships of slo

• Slob binds to and modulates the Drosophila Slowpoke (dSlo) calcium-activated potassium channel and also recruits the ubiquitous signaling protein 14-3-3 to the channel regulatory complex [18].
• Similarly, the slowpoke mutation significantly suppresses the increased transmitter release conferred either by a mutation in Shaker or by application of 4-aminopyridine, which blocks the Shaker-encoded potassium channel at the Drosophila nerve terminal [10].
• Verification using real-time PCR shows that pan-neuronal expression of eve is sufficient to repress transcripts for both slo and nAcRalpha-96Aa [19].

Other interactions of slo

• 3. Confocal fluorescence microscopy demonstrates that Slob and dSlo redistribute in cotransfected cells and are colocalized in large intracellular structures [16].
• These data, taken together, suggest that monomeric D14-3-3zeta is capable of modulating dSlo channel activity in this regulatory complex [20].
• Current-clamp recordings from normal, Sh, slo and the double-mutant Sh;slo fibers suggested that ICF plays a stronger role than IA in repolarization of the larval muscle membrane [13].
• Anesthetic sensitivity was also examined in mutant strains of D.m. which express abnormalities either in other potassium channel conductances (eag, slo) or other ion conductances (para) [21].
• The dSLIP1 and dSlo mRNAs are expressed coincidently throughout the Drosophila nervous system, the two proteins interact in vitro, and they may be coimmunoprecipitated from transfected cells [8].

Analytical, diagnostic and therapeutic context of slo

• To further investigate this notion, we performed a sequence analysis of the alpha-subunit of cloned slowpoke KCa channels from Drosophila and mammals [22].
• Cloned large conductance Ca2+-activated K+ channels (BK or maxi-K+ channels) from Drosophila (dSlo) were expressed in Xenopus oocytes and studied in excised membrane patches with the patch-clamp technique [23].

References