Abstract
Single-channel kinetics has proven a powerful tool to reveal information about the gating mechanisms that control the opening and closing of ion channels. This introductory review focuses on the gating of large conductance Ca2+- and voltage-activated K+ (BK or Slo1) channels at the single-channel level. It starts with single-channel current records and progresses to presentation and analysis of single-channel data and the development of gating mechanisms in terms of discrete state Markov (DSM) models. The DSM models are formulated in terms of the tetrameric modular structure of BK channels, consisting of a central transmembrane pore-gate domain (PGD) attached to four surrounding transmembrane voltage sensing domains (VSD) and a large intracellular cytosolic domain (CTD), also referred to as the gating ring. The modular structure and data analysis shows that the Ca2+ and voltage dependent gating considered separately can each be approximated by 10-state two-tiered models with five closed states on the upper tier and five open states on the lower tier. The modular structure and joint Ca2+ and voltage dependent gating are consistent with a 50 state two-tiered model with 25 closed states on the upper tier and 25 open states on the lower tier. Adding an additional tier of brief closed (flicker states) to the 10-state or 50-state models improved the description of the gating. For fixed experimental conditions a channel would gate in only a subset of the potential number of states. The detected number of states and the correlations between adjacent interval durations are consistent with the tiered models. The examined models can account for the single-channel kinetics and the bursting behavior of gating. Ca2+ and voltage activate BK channels by predominantly increasing the effective opening rate of the channel with a smaller decrease in the effective closing rate. Ca2+ and depolarization thus activate by mainly destabilizing the closed states.
Highlights
Large conductance Ca2+- and voltage activated K+ channels are widely distributed
The joint activation by Ca2+ and voltage is obtained with five repeats of the 10-state voltage activation mechanism, where each repeat has 0, 1, 2, 3, or 4 bound Ca2+
The joint activation can be obtained with five repeats of the 10-state Ca2+ activation mechanism, where each repeat has 0, 1, 2, 3, or 4 activated voltage sensors
Summary
Large conductance Ca2+- and voltage activated K+ channels ( referred to as Slo or maxi K+ channels) are widely distributed. There have been a number of recent reviews on the gating mechanisms of BK channels (Magleby, 2003; Cox, 2005, 2007; Latorre and Brauchi, 2006; Cui et al, 2009; Latorre et al, 2010; Lee and Cui, 2010; Horrigan, 2012; Contreras et al, 2013; Hoshi et al, 2013) To supplement these reviews, we will take a different approach for our contribution to the Frontiers in Physiology Research Topic: BK channels: integrators of cellular signals in health and disease. Representative figures of single-channel data and analysis are included so that the review is relatively self-contained Those who seek further information about gating mechanism after reading this introductory single-channel review can start with the extensive reference lists found in the reviews listed above. The inside of the excised patch of membrane in the tip of a glass pipette is exposed to the bath solution, allowing the solution at the inner membrane www.frontiersin.org
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
