CELLS OF THE NERVOUS SYSTEM AND ELECTRICAL STIMULATION - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 617

dependency on or the quantity of secreted NGF. These relationships help deter-
mine the mechanisms or pathways through which electrical stimulation alters cell
behavior.
18.6 NEURONS IN ELECTRIC FIELDS
Despite the different cell types investigated using electrical stimulation, neurons
are probably the most thoroughly researched in this context, with myocardial
cells following the lead. The relationship between neurons and EFs has been
investigated, mostly using neurons derived from cold-blooded animals, which
eliminates the need for equipment such as temperature and CO 2 controlled
incubators.
The work of McCaig et al. on spinal cord neurons from embryonic frogs
( Xenopus laevis ) using an agar bridge setup (McCaig et al. 2005) is a great
example. McCaig et al. investigated the effects of EFs on axon guidance or turning,
axonal growth rate, growth cone receptors, secondary messengers and cytoskele-
tal proteins.
18.6.1 Axon Guidance
Galvanotropism occurs at different thresholds for different cells types (Nuccitelli
2003). The same can be said about the different types of neurons and the strength
of the EF needed to initiate neurites turning. Thresholds as low as 7 mV/mm have
been reported to initiate neurite growth cone turning (Nuccitelli 2003). If neurite
turning were dependent only on EF strength, then determining an underlying
mechanism would not be such a daunting task.
Surface adhesion molecules or extracellular matrix components effect the
infl uence an EF has on cells (Rajnicek et al. 1998). Laminin is often applied after
another surface adhesion protein such as poly L-lysine (PLL) or poly L-ornithine.
Neurons examined by Rajnicek et al. turned cathodally in the presence of an
EF on culture plastic (control). Neurite on laminin or on PLL with laminin
remained cathodal, although not as prominent as on culture plastic. However, on
PLL, neurite growth under an EF changed direction (compared to control)
toward the anode (Rajnicek et al. 1998). PLL is strongly cationic demonstrating
neurite galvanotropism (guidance due to an EF) to be dependent on surface
charge, but surface charge alone was not suffi cient to cause a complete change in
growth.
A misconception can be that neurites turn towards the cathode because most
experiments were carried out using embryonic Xenopus neurons to demonstrate
neurites are directed towards the cathode in an EF (McCaig et al. 1994) (Figure
18.4). Yet, cathodal turning has been shown mainly for motor neurons (Hinkle
et al. 1981) and for cold blooded animals such as Xenopus . However, the direction
towards which neurites extend varies for other neuronal cell types. For example,
processes from sensory neurons do not turn (Jaffe and Poo 1979), and neurites