INOR 202

The mammalian BK channels (large conductance, calcium-activated potassium channels) restrict calcium influx and excitability, and they are involved in many biologically important processes, such as mitochondrial homeostasis, blood pressure regulation, and cytoprotection from ischemia where heme stress may be particularly crucial. We have discovered that nanomolar levels of heme can inhibit the flow of potassium ions through these mammalian Slo1 BK channels. We cloned and overexpressed a segment of the regulatory, cytoplasmic domain of the humanSlo channel and looked how it binds heme. Our experiments with wild-type and variant indicate that heme may bind to a specific CXXCH motif that is located near the calcium binding regulatory domain. Therefore, heme may play an important role in the regulation of mammalian BK channels.