Video Experimental Relacionado

Updated: Jan 31, 2026

Study of Cell Migration in Microfabricated Channels

Study of Cell Migration in Microfabricated Channels

Published on: February 21, 2014

Inhibición excepcionalmente selectiva de los canales Na_V1.5 por captura del sensor de voltaje mediante

Mahdi Jamili¹, Marwa Ahmed¹, Alisa Bernert¹

¹Department of Biophysics, Center for Molecular Biomedicine, Friedrich Schiller University Jena and Jena University Hospital, Hans-Knöll-Straße 2, 07745, Jena, Germany.

Scientific reports

|January 29, 2026

Abstract:

The human voltage-gated sodium channel hNa_V1.5 is essential for cardiac excitability. Though underrecognized, Na_V1.5 is also expressed in multiple cancers, promoting cell migration and malignancy. hNa_V1.5 is a therapeutic target but limited pharmacological isoform specificity presents a risk of side effects via neuronal and skeletal muscle Na_V channels. Here we identify Mg²⁺-protoporphyrin IX (MgPpIX), a Mg-containing tetrapyrrole and intermediate in chlorophyll biosynthesis, as a potent inhibitor of hNa_V1.5 (IC₅₀ of 1 nM). The activity profile of various metal protoporphyrins correlates with the electrostatic potential at the metal center of the compounds. MgPpIX is specific to hNa_V1.5, as no inhibition of other hNa_V isoforms (hNa_V1.2, 1.4, 1.7, 1.8) was detected. A mutagenesis study and structural modeling reveals that MgPpIX stabilizes the domain-II voltage sensor in the deactivated conformation, with residues E795 and N803 being relevant determinants. MgPpIX also inhibits native Na_V channels in breast cancer MDA-MB-231 and colorectal carcinoma SW-480 cell lines, and suppresses cell migration. MgPpIX is an exceptionally potent and specific inhibitor of hNa_V1.5 and may serve as a lead compound in anti-cancer drug development.

Palabras clave:

SCN5A Cáncer Canal de sodio cardíaco Potencial de superficie electrostática Protoporfirina metálica Dinámica molecular Sensor de voltaje

Más Videos Relacionados

Author Spotlight: Exploring the Role of Ion Channels in Cancer: Characterization and Potential Treatment Approaches

Author Spotlight: Exploring the Role of Ion Channels in Cancer: Characterization and Potential Treatment Approaches

Published on: June 16, 2023

Evaluation of Cancer Stem Cell Migration Using Compartmentalizing Microfluidic Devices and Live Cell Imaging

Evaluation of Cancer Stem Cell Migration Using Compartmentalizing Microfluidic Devices and Live Cell Imaging

Published on: December 23, 2011

Videos de Conceptos Relacionados

Voltage-gated Ion Channels

Voltage-gated Ion Channels

Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...

Exceptions to the Octet Rule

Exceptions to the Octet Rule

Many covalent molecules have central atoms that do not have eight electrons in their Lewis structures. These molecules fall into three categories:

Cancer Cell Migration through Invadopodia

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...

Ion Channels

Ion Channels

The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
Ion channels are specialized integral membrane proteins on the plasma membrane that allow...

Cell Migration

Cell Migration

Cell migration is a process by which the cells move from one location to another, playing an essential role in embryological development, repair and regeneration, immune response, and metastasis. Cells migrate in response to chemical or mechanical signals generated by specific organs or tissues. The overall mechanism includes three steps - polarization, protrusion, and release. Polarization involves the formation of a distinct cell front and rear, which determines the direction of movement.

Cell Migration

Cell Migration

Cell migration, the process by which cells move from one location to another, is essential for the proper development and viability of organisms throughout their life. When cells are not able to migrate properly to their ordained locations, various disorders may occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis.