Gating kinetics of Ca2+-activated K+ channels from rat muscle incorporated into planar lipid bilayers. Evidence for two voltage-dependent Ca2+ binding reactions.

Moczydlowski, Edward; Latorre, Ramón

doi:10.1085/jgp.82.4.511

Cited by 372 publications

(333 citation statements)

References 29 publications

Supporting

Mentioning

273

Contrasting

Order By: Relevance

“…These include ligand-gated channels for glutamate (Patlak et al, 1979) and GABA (Macdonald and Twyman, 199 1) as well as voltage-gated channels such as Na channels (Patlak and Ortiz, 1986;Nilius, 1988;Moorman et al, 1990;Zhou et al, 1991) and Ca*+-activated K+ channels (Moczydlowski and Latorre, 1983;McManus and Magleby, 1988). Modal changes in both activation and inactivation kinetics have been reported.…”

Section: Discussionmentioning

confidence: 99%

Multiple modes of N-type calcium channel activity distinguished by differences in gating kinetics

1993

View full text Add to dashboard Cite

In many neurons, N-type Ca2+ channels are a major Ca2+ entry pathway and strongly influence neurotransmitter release. We carried out cell- attached patch recordings (110 mM Ba2+ as charge carrier) to characterize the rapid opening and closing kinetics of N-type Ca2+ channel gating in frog sympathetic neurons. Single channels display at least three distinct patterns of gating, characterized as low-, medium- , and high-rho o modes on the basis of channel open probability (rho o) during depolarizing pulses to -10 mV. Spontaneous transitions from one mode to another are infrequent, with an exponential distribution of dwell times and mean sojourns of approximately 10 sec in each mode. Thus, a channel typically undergoes hundreds or thousands of open- closed transitions in one mode before switching to a different mode. Transitions between modes during a depolarization were occasionally detected, but were rare, as expected for infrequent modal switching. Within each mode, the activation kinetics were well described by a simple scheme (C2-C1-O), as previously reported for other types of Ca2+ channels. Rate constants are strikingly different from one mode to another, giving each mode its own characteristic kinetic signature. The gating behavior at -10 mV ranges from brief openings (approximately 0.3 msec) and long closures (10–20 msec) for low-rho o gating to long openings (3 msec) and brief closures (approximately 1 msec) for high- rho o gating. Intermediate values for mean open durations (approximately 1.5 msec) and mean closed durations (approximately 3 msec) were found for medium-rho o gating. In addition to being kinetically distinct, channel openings in the low-rho o mode often exhibit a unitary current approximately 0.2 pA larger than in the medium- or high-rho o mode. Each mode is characterized by its own voltage dependence: activation occurs at relatively negative potentials and is most steeply voltage dependent in the high-rho o mode, while activation requires very strong depolarizations and is weakly voltage dependent in the low-rho o mode. The proportion of time spent in the individual modes varies greatly from one patch to another, suggesting that modal gating may be subject to cellular control.

show abstract

Section: Discussionmentioning

confidence: 99%

Multiple modes of N-type calcium channel activity distinguished by differences in gating kinetics

1993

View full text Add to dashboard Cite

show abstract

“…The Horrigan-Aldrich model suggests that GoSlo-SR-5-6 works by stabilizing the open conformation of the channel and the activated state of the voltage sensors, yet decouples the voltage sensors from the pore gate. -activated K + (BK) channels are poreforming transmembrane proteins and are allosterically modulated by voltage and Ca 2+ (1)(2)(3)(4)(5). The BKα subunits form tetramers, and both regulatory β-(6) and γ-subunits (7) can associate with the pore-forming α-subunits.…”

Section: +mentioning

confidence: 99%

Molecular mechanisms underlying the effect of the novel BK channel opener GoSlo: Involvement of the S4/S5 linker and the S6 segment

Webb

Kshatri

Large

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

GoSlo-SR-5-6 is a novel large-conductance Ca 2+ -activated K + (BK) channel agonist that shifts the activation V 1/2 of these channels in excess of −100 mV when applied at a concentration of 10 μM. Although the structure-activity relationship of this family of molecules has been established, little is known about how they open BK channels. To help address this, we used a combination of electrophysiology, mutagenesis, and mathematical modeling to investigate the molecular mechanisms underlying the effect of GoSlo-SR-5-6. Our data demonstrate that the effects of this agonist are practically abolished when three point mutations are made: L227A in the S4/S5 linker in combination with S317R and I326A in the S6C region. Our data suggest that GoSlo-SR-5-6 interacts with the transmembrane domain of the channel to enhance pore opening. The Horrigan-Aldrich model suggests that GoSlo-SR-5-6 works by stabilizing the open conformation of the channel and the activated state of the voltage sensors, yet decouples the voltage sensors from the pore gate.

show abstract

“…Of the ion channels in the voltage-dependent K ϩ channel family, large-conductance Ca 2ϩ -and voltage-regulated K ϩ channels (Slo1 BK-type) are largely unique in the extent to which channel opening is independently regulated by two physiological signals: membrane voltage and cytosolic Ca 2ϩ (Barrett et al, 1982;Moczydlowski and Latorre, 1983). Understanding how two distinct physiological signals each regulate channel opening is likely to be particularly informative about the mechanical linkages that can act either independently or in concert to influence channel activation.…”

Section: Introductionmentioning

confidence: 99%

Ligand-Dependent Activation of Slo Family Channels Is Defined by Interchangeable Cytosolic Domains

Xia¹,

Zhang²,

Lingle³

2004

J. Neurosci.

View full text Add to dashboard Cite

Gating kinetics of Ca2+-activated K+ channels from rat muscle incorporated into planar lipid bilayers. Evidence for two voltage-dependent Ca2+ binding reactions.

Cited by 372 publications

References 29 publications

Multiple modes of N-type calcium channel activity distinguished by differences in gating kinetics

Multiple modes of N-type calcium channel activity distinguished by differences in gating kinetics

Molecular mechanisms underlying the effect of the novel BK channel opener GoSlo: Involvement of the S4/S5 linker and the S6 segment

Ligand-Dependent Activation of Slo Family Channels Is Defined by Interchangeable Cytosolic Domains

Contact Info

Product

Resources

About