Related Experiment Video

Updated: Jul 11, 2025

Patch Clamp and Perfusion Techniques for Studying Ion Channels Expressed in Xenopus oocytes
10:19

Patch Clamp and Perfusion Techniques for Studying Ion Channels Expressed in Xenopus oocytes

Published on: January 10, 2011

21.0K

Progesterone activation of β1-containing BK channels involves two binding sites

Kelsey C North1, Andrew A Shaw1, Anna N Bukiya1

  • 1Department of Pharmacology, Addiction Science, and Toxicology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, 38103, USA.

Nature Communications
|November 9, 2023
PubMed

Insights

Progesterone activates brain blood vessel BK channels, aiding recovery from cerebral ischemia. This action involves specific binding sites on BK channel regulatory subunits, offering new therapeutic targets.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Progesterone (≥1 µM) aids cerebral ischemia recovery, potentially via cerebrovascular dilation.
  • The specific molecular targets of progesterone's cerebrovascular effects remain unidentified.
  • Cerebrovascular smooth muscle cells express large-conductance calcium-activated potassium (BK) channels.

Purpose of the Study:

  • To identify the molecular targets of progesterone action in cerebrovascular myocytes.
  • To elucidate the mechanism by which progesterone activates BK channels.
  • To investigate the role of BK channel regulatory subunits in progesterone-mediated cerebrovascular effects.

Main Methods:

  • Electrophysiological recordings (e.g., patch-clamp) of mouse cerebrovascular myocytes and heterologous expression systems.
  • Site-directed mutagenesis of BK channel α and β1/β4 regulatory subunits.
  • In vivo and in vitro studies assessing cerebrovascular responses to progesterone and alcohol.

Main Results:

  • Micromolar progesterone activates BK channels in mouse cerebrovascular myocytes, dependent on β1 and β4 subunits.
  • Progesterone binds to conserved steroid binding sites on β1/β4 subunits, with distinct high-affinity and low-affinity sites.
  • Mutations in key residues (Trp87, Tyr32, Trp163) of the β1 subunit abolish progesterone-induced channel activation and cerebrovascular dilation.

Conclusions:

  • Progesterone activates cerebrovascular BK channels through a mechanism involving both high- and low-affinity binding sites on β1/β4 regulatory subunits.
  • This activation is crucial for progesterone-mediated cerebrovascular dilation and recovery from cerebral ischemia.
  • Progesterone counteracts alcohol-induced cerebrovascular constriction, suggesting therapeutic potential.

More Related Videos

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting10:08

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting

Published on: December 9, 2022

2.2K
Mutagenesis and Functional Analysis of Ion Channels Heterologously Expressed in Mammalian Cells15:28

Mutagenesis and Functional Analysis of Ion Channels Heterologously Expressed in Mammalian Cells

Published on: October 1, 2010

17.5K

Related Concept Videos

G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
4.6K
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
7.2K
Adrenergic Receptors: β Subtype01:26

Adrenergic Receptors: β Subtype

β-adrenoceptors have varied sensitivities towards adrenaline, noradrenaline, and isoprenaline. The order of agonist potency is as follows:
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...
1.7K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.6K
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.2K
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.3K