Calcium-activated potassium channel subunit alpha-1 (KCa1.1) (KCa1.1)

The Calcium-activated potassium channel subunit alpha-1 (KCa1.1), also known as the SLO-1 or BK channel, is a large-conductance ion channel uniquely regulated by both intracellular calcium concentrations and membrane voltage [1, 2]. It is widely expressed across diverse tissues, particularly in the central nervous system and smooth muscle, where it serves as a critical negative feedback regulator that dampens cellular excitability by facilitating potassium efflux and membrane hyperpolarization [11, 12, 16]. In humans, mutations in the encoding gene KCNMA1 are associated with KCNMA1-linked channelopathy, a range of neurological disorders including epilepsy, paroxysmal nonkinesigenic dyskinesia, and cerebellar ataxia [15, 17, 18]. The channel is a significant pharmacological target; notably, it is the primary site of action for the anthelmintic drug emodepside, which paralyzes parasitic nematodes by activating their SLO-1 channels [5, 13]. While various BK channel openers like BMS-204352 have been explored for neuroprotection in stroke and for treating hypertension, achieving sufficient tissue specificity remains a key challenge for drug development [1, 14, 21].

Other names

Slo1BK channelMaxi-K channelKCNMA1Slowpoke homolog 1KCa1.1BKCa

Pharmacological activation (opening) to induce hyperpolarization and reduce cellular excitability, or inhibition (blocking) to prevent potassium efflux and modulate repolarization.