ABSTRACT
Spontaneous rhythmic activity of pacemaker neurons in the central nervous system underlies fundamental neurological processes such as locomotion, cognition and circadian rhythm. Among the wide range of ion channels required for its generation, the Ca2+-activated K+(KCa) channels play a prominent role in maintaining physiologically-relevant frequency and pattern of pacemaker activity. Much of our understanding of the functions of KCa channels in pacemaker neurons have been derived from pharmacological studies using channel modulators, such as iberiotoxin and apamin. Despite the significant advances made, recent studies have painted an increasingly complex picture of the effects of widely used KCa channel modulators on unintended targets that may confound our under?standing of their functions. In this review, we discussed the utility and shortcomings of the KCa channel modulators, and highlighted the significance of these findings, because the KCa channel modulators have been used in early clinical trials to treat disorders ranging from Parkinson disease to alcoholism.