Large conductance calcium-activated potassium channel SLO-1 (SLO-1)

The Large conductance calcium-activated potassium channel SLO-1, also known as the BK channel, is a critical regulator of cellular excitability in both neurons and muscle cells [1, 13]. It is uniquely gated by both membrane depolarization and increases in intracellular calcium concentration, allowing it to integrate electrical and chemical signals to modulate repolarization [13, 18]. In nematodes, SLO-1 is the primary molecular target for the anthelmintic drug emodepside, which activates the channel to cause hyperpolarization and flaccid paralysis [2, 3]. While essential for parasite control, the channel's human ortholog, KCNMA1, is involved in vital processes such as smooth muscle relaxation and neurotransmitter release [13, 16]. Consequently, therapeutic strategies targeting SLO-1 must achieve high selectivity to avoid host toxicities associated with human BK channel dysfunction, such as epilepsy or movement disorders [13, 16]. Therapeutic development focuses on exploiting structural differences between nematode and mammalian channels to ensure safety [2, 12].

Other names

BK channelMaxi-K channelKCa1.1Slowpoke homolog 1KCNMA1Calcium-activated potassium channel subunit alpha-1

Emodepside acts as a potent activator of the SLO-1 channel, increasing its open probability and leading to a massive efflux of potassium ions. This causes membrane hyperpolarization, which inhibits neuronal and muscle activity, resulting in flaccid paralysis and death of the nematode [1, 2, 4].