CELLS OF THE NERVOUS SYSTEM AND ELECTRICAL STIMULATION - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 619

Since more than one type of AChR exists, the dependency of neurite guid-
ance on nicotinic and muscarinic AChR in an EF was tested. When nicotinic
AChRs were blocked with D-tubocurare cathodal turning did not occur, but
when muscarinic AChRs were blocked with the antagonist atropine and/or
suramin, cathodal turning was enhanced (Erskine and McCaig 1995). Atropine
and suramin are also P2-purinoceptor and bFGF receptor antagonists. Therefore,
the interaction of P2-purinoceptors and bFGF receptors with an EF cannot be
ruled out.
The release of ACh can be enhanced using neurotrophins NT-3 and brain
derived neurotorphic factor (BDNF) as demonstrated in embryonic Xenopus
neuromuscular synapses. The addition of either NT-3 or BDNF to media of
cells grown in an EF enhanced growth cone attraction three-fold at 150 mV/mm,
and also reduced the threshold required for cathodal guidance. This effect was
shown to be dependent on trkB and trkC receptors by blocking NT-3-trk receptor
interaction using antagonist K252a. Not all growth factors tested enhanced
growth cone turning, for example, nerve growth factor (NGF) and ciliary
neuronotrophic factor (CNTF) had no affect on growth cone guidance (McCaig
et al. 2000).
These results implicate three receptors in the regulation of EF induced
growth cone turning or nuerite guidance: P2-purinoceptor, bFGF receptor and
AChR. Therefore, there does not seem to be a single receptor responsible for
galvanotaxis or growth cone guidance by an EF. Instead, combinations of signals
dictate whether cells are guided by an EF.

18.6.3 Receptor Accumulation and Autoregulation
The accumulation of membrane receptors in an EF is not precisely understood.
However, electrophoresis and electroosmosis have been experimentally and the-
oretically shown to be driving forces in the migration of membrane bound pro-
teins due to an EF. Briefl y, most membrane receptors are proteins with an overall
negative charge, which electrophoretic force dictates should accumulate towards
the anode (+) facing side of the membrane (Jaffe 1977). Yet, water molecules are
polar and surround negatively-charged proteins. The surrounding positively
charged water molecules cause the proteins to migrate toward the cathode (

).
This is known as electroosmosis. Thus, electroosmosis counteracts the electropho-
retic effect when proteins are negatively charged, which is usually the case. More
on this theory can be explored in an interesting article on macromolecular move-
ment on the membranes of cells by McLaughlin and Poo (McLaughlin and
Poo 1981 ).
When receptors bind their ligands, a conformational change usually occurs,
which can change how the receptor migrates in an EF (possibly due to changes in
the proteins overall charge). Therefore, cells sometimes do not respond to an
applied EF if ligands are bound to their receptors. This was demonstrated using
concanavalin A (Con A), which recognizes a commonly occurring sugar structure,
(

−

α -linked mannose, found in many membrane bound glycoproteins. The use of