Calcium-activated K+ channels: Metabolic regulation

Calcium-activated potassium (K_Ca) channels are highly modulated by a large spectrum of metabolites. Neurotransmitters, hormones, lipids, and nucleotides are capable of activating and/or inhibiting K_Ca channels. Studies from the last few years have shown that metabolites modulate the activity of K_Ca channels via: (1) a change in the affinity of the channel for Ca²⁺ (K_1/2 is modified), (2) a parallel shift in the voltage axis of the acitvation curves, or (3) a change in the slope (effective valence) of the voltage dependence curve. The shift of the voltage dependence curve can be a direct consequence of the change in the affinity for Ca²⁺. Recently, the mechanistic steps involved in the modulation of K_Ca channels are being uncovered. Some interactions may be direct on K_Ca channels and others may be mediated via G-proteins, second messengers, or phosphorylation. The information given in this review highlights the possibility that K_Ca channels can be activated or inhibited by metabolites without a change in the intracellular Ca²⁺ concentration.