Response of nerve growth cone to focal electric currents

Abstract

Monopolar electric current pulses were focally applied through a micropipette to the growth cone of Xenopus embryonic neurons in culture. Application of the current directly in front of the growth cone modulated the rate of growth cone extension: Negative (sink) currents increased the growth rate, while positive (source) currents reduced the growth rate. When the currents were applied in a direction perpendicular to the direction of the neurite growth, both negative and positive currents produced inhibitory effects. Application of a negative focal current at a 45 degree angle with respect to the direction of neurite growth resulted in an oriented growth of the neurite toward the current sink. However, after the growth cone had been attracted to the vicinity of a current sink, further extension of the neurite was inhibited. These current effects occur rapidly after the onset of the current application, and are at least partially reversible within 1 hr after the termination of the current. The magnitude of current density required to induce a growth cone response was found to be in the order of a few pA per micron2. Such current density is close to that which may be generated at the muscle cell surface by the acetylcholine molecules released from the growth cone during the early phase of nerve-muscle contact.

Prospects on clinical applications of electrical stimulation for nerve regeneration

“…Moreover, this growth is consistently oriented to the cathode. Patel et al [1985] applied electric pulses (pA/ J.LV) focally near growth cones of Xenopus neurons and noted directional growth toward the negative (sink) electrode. Both steady and pulsatile fields have been found to be effective in promoting directed neurite outgrowth despite the endogenous occurrence of pulsatile fields.…”

D1-type dopamine receptors inhibit growth cone motility in cultured retina neurons: evidence that neurotransmitters act as morphogenic growth regulators in the developing central nervous system.

“…Three types of extracellular cues have long been considered likely candidates for controlling neurite growth: (i) physical guidance (6,11,12), (ii) spatial/temporal gradients of diffusible (13)(14)(15)(16)(17) or bound (17-23) neurite growthpromoting molecules, and (iii) electric fields (24)(25)(26)(27). The possibility has been raised that neurotransmitters also might play a role (28), as it has been reported that certain cultured neurons isolated from the snail Helisoma stop neurite regeneration in response to serotonin or dopamine (29)(30)(31).…”

D1-type dopamine receptors inhibit growth cone motility in cultured retina neurons: evidence that neurotransmitters act as morphogenic growth regulators in the developing central nervous system.

“…Growth cones provide sites for new membrane addition (1, 9, 10) needed in neurite elongation, and they control the direction and extent of elongation (2, 3) through processes still poorly understood. Ultimately, growth cones become quiescent and disappear as final patterns of arborization are achieved.Three types of extracellular cues have long been considered likely candidates for controlling neurite growth: (i) physical guidance (6,11,12), (ii) spatial/temporal gradients of diffusible (13-17) or bound (17-23) neurite growthpromoting molecules, and (iii) electric fields (24)(25)(26)(27). The possibility has been raised that neurotransmitters also might play a role (28), as it has been reported that certain cultured neurons isolated from the snail Helisoma stop neurite regeneration in response to serotonin or dopamine (29-31).…”

“…Three types of extracellular cues have long been considered likely candidates for controlling neurite growth: (i) physical guidance (6,11,12), (ii) spatial/temporal gradients of diffusible (13)(14)(15)(16)(17) or bound (17-23) neurite growthpromoting molecules, and (iii) electric fields (24)(25)(26)(27). The possibility has been raised that neurotransmitters also might play a role (28), as it has been reported that certain cultured neurons isolated from the snail Helisoma stop neurite regeneration in response to serotonin or dopamine (29)(30)(31).…”