Animal cells connected by nanotubes can be electrically coupled through interposed gap-junction channels

Area of Science:

• Cell Biology
• Neuroscience
• Biophysics

Background:

• Tunneling nanotubes (TNTs) are emerging conduits for intercellular communication.
• These actin-based membrane tubes facilitate the exchange of molecules and organelles.
• The role of TNTs in electrical signal propagation remained largely unexplored.

Purpose of the Study:

• To investigate the capacity of TNTs to mediate electrical signal transmission between cells.
• To determine the mechanisms underlying TNT-mediated electrical coupling.
• To explore the downstream consequences of TNT-dependent electrical synchronization.

Main Methods:

• Optical membrane-potential measurements and whole-cell patch-clamp recordings were employed.
• Mechanical stimulation was used to assess signal propagation.
• Immunoreactivity for connexin 43 and pharmacological blockers (meclofenamic acid, mibefradil) were utilized.

Main Results:

• TNTs facilitated bidirectional electrical signal spread between connected rat kidney cells over 10-70 μm.
• Electrical coupling strength correlated with TNT length and number.
• Evidence implicated gap junctions in TNT-mediated electrical coupling, as seen in connexin 43 localization and blocker sensitivity.
• TNT-mediated depolarization induced calcium influx via low voltage-gated Ca(2+) channels in HEK293 cells.

Conclusions:

• TNTs serve as functional electrical conduits, enabling long-distance cell-to-cell communication.
• Gap junctions at the TNT-cell interface are crucial for this electrical coupling.
• TNT-mediated electrical synchronization can activate downstream signaling pathways, such as calcium influx.