Defining the BK channel domains required for beta1-subunit modulation

Background & Objective: The large conductance calcium-activated potassium (BK) channel, extensively distributed in the central nervous system (CNS), is considered as a vital player in the pathogenesis of epilepsy, with evidence implicating derangement of K+ as well as regulating action potential shape and duration. However, unlike other channels implicated in epilepsy whose function in neurons could clearly be labeled “excitatory” or “inhibitory”, the unique physiological behavior of the BK channel allows it to both augment and decrease the excitability of neurons. Thus, the role of BK in epilepsy is controversial so far, and a growing area of intense investigation. Conclusion: Here, this review aims to highlight recent discoveries on the dichotomous role of BK channels in epilepsy, focusing on relevant BK-dependent pro- as well as antiepileptic pathways, and discuss the potential of BK specific modulators for the treatment of epilepsy.

Download Full-text

BK channel openers inhibit migration of human glioma cells

Pflügers Archiv - European Journal of Physiology ◽

10.1007/s00424-003-1012-4 ◽

2003 ◽

Vol 446 (2) ◽

pp. 248-255 ◽

Cited By ~ 50

Author(s):

Robert Kraft ◽

Peter Krause ◽

Silke Jung ◽

Daniel Basrai ◽

Lutz Liebmann ◽

...

Keyword(s):

Glioma Cells ◽

Bk Channel ◽

Human Glioma ◽

Human Glioma Cells

Download Full-text

Large-conductance voltage- and Ca2+-activated K+ channel regulation by protein kinase C in guinea pig urinary bladder smooth muscle

AJP Cell Physiology ◽

10.1152/ajpcell.00325.2013 ◽

2014 ◽

Vol 306 (5) ◽

pp. C460-C470 ◽

Cited By ~ 18

Author(s):

Kiril L. Hristov ◽

Amy C. Smith ◽

Shankar P. Parajuli ◽

John Malysz ◽

Georgi V. Petkov

Keyword(s):

Smooth Muscle ◽

Membrane Potential ◽

Guinea Pig ◽

Bk Channels ◽

Bk Channel ◽

K Channel ◽

Channel Activity ◽

Open Probability ◽

Channel Regulation ◽

Pkc Activation

Large-conductance voltage- and Ca2+-activated K+ (BK) channels are critical regulators of detrusor smooth muscle (DSM) excitability and contractility. PKC modulates the contraction of DSM and BK channel activity in non-DSM cells; however, the cellular mechanism regulating the PKC-BK channel interaction in DSM remains unknown. We provide a novel mechanistic insight into BK channel regulation by PKC in DSM. We used patch-clamp electrophysiology, live-cell Ca2+ imaging, and functional studies of DSM contractility to elucidate BK channel regulation by PKC at cellular and tissue levels. Voltage-clamp experiments showed that pharmacological activation of PKC with PMA inhibited the spontaneous transient BK currents in native freshly isolated guinea pig DSM cells. Current-clamp recordings revealed that PMA significantly depolarized DSM membrane potential and inhibited the spontaneous transient hyperpolarizations in DSM cells. The PMA inhibitory effects on DSM membrane potential were completely abolished by the selective BK channel inhibitor paxilline. Activation of PKC with PMA did not affect the amplitude of the voltage-step-induced whole cell steady-state BK current or the single BK channel open probability (recorded in cell-attached mode) upon inhibition of all major Ca2+ sources for BK channel activation with thapsigargin, ryanodine, and nifedipine. PKC activation with PMA elevated intracellular Ca2+ levels in DSM cells and increased spontaneous phasic and nerve-evoked contractions of DSM isolated strips. Our results support the concept that PKC activation leads to a reduction of BK channel activity in DSM via a Ca2+-dependent mechanism, thus increasing DSM contractility.

Download Full-text