SLO, SLO, quick, quick, slow: calcium-activated potassium channels as regulators of Caenorhabditis elegans behaviour and targets for anthelmintics.
Large-conductance calcium and voltage-activated potassium channels, termed SLO-1 (or BK), are pivotal players in the regulation of cell excitability across the animal phyla. Furthermore, emerging evidence indicates that these channels are key mediators of a number of neuroactive drugs, including the most recent new anthelmintic, the cyclo-octadepsipeptide emodepside. Detailed reviews of the structure, function and pharmacology of BK channels have recently been provided (Salkoff et al. in Nat Rev Neurosci 7:921-931, 2006; Ghatta et al. in Pharmacol Ther 110:103-116, 2006) and therefore these aspects will only briefly be covered here. The purpose of this review is to discuss how SLO-1 channels might function as regulators of neural transmission and network activity. In particular, we focus on the role of SLO-1 in the regulation of Caenorhabditis elegans behaviour and highlight the role of this channel as an effector for pleiotropic actions of neuroactive drugs, including emodepside. On the premise that C. elegans is a 'model nematode' with respect to many aspects of neural function, the intention is that this might inform a broader understanding of the role of these channels in the nematodes and their potential as novel anthelmintic targets.
Holden-Dye
Lindy
L
School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, SO16 7PX, UK. lmhd@soton.ac.uk
O'Connor
Vincent
V
Hopper
Neil A
NA
Walker
Robert J
RJ
Harder
Achim
A
Bull
Kathryn
K
Guest
Marcus
M
D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D001522:Behavior, Animal / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000871:Anthelmintics; D029742:Caenorhabditis elegans Proteins; D051036:Large-Conductance Calcium-Activated Potassium Channels; C494845:slo-1 protein, C elegans; D002118:Calcium