Perturbation of the direction of neurite growth by pulsed and focal electric fields

Abstract

We have studied the orientation of neurite growth in the culture of embryonic Xenopus neurons in response to three types of extracellular electric fields: spatially uniform pulsed fields, focally applied steady (DC) fields, and focally applied pulsed fields. Under uniform pulsed fields, neurites showed a preferential orientation toward the cathode pole of the field in a manner similar to that previously found for DC fields. The extent of neurite orientation depended upon the duration, amplitude, and frequency of the pulse but appeared to be similar to that produced by a uniform DC field of an equivalent time-averaged field intensity. For square pulses of 5 msec duration, the minimal amplitude and frequency required to produce a detectable orientation of neurite growth over a period of 24 hr were 2.5 V/cm and 10 Hz, which correspond to a time-averaged field intensity of 125 mV/cm. Steady or pulsed focal fields were applied by passing a current through a micropipette placed near the growth cone of the neurite. Fields of negative polarity (current sink) were found to attract the growth cone, whereas fields of positive polarity (current source) were found to deflect the growth cone away from the pipette. The threshold DC current density needed at the growth cone to perturb its direction of growth within 15 min was 0.2 to 2 pA/micron2 (or 3 to 30 mV/cm); and for focal pulsed currents (pulse duration 5 msec), a typical combination of minimal pulse amplitude and frequency was 4 pA/micron2 and 10 Hz. This threshold focal current is similar to that which occurs at the synaptic cleft during active synaptic activity.

Aberrant Patterning of Neuromuscular Synapses in Choline Acetyltransferase-Deficient Mice

“…That is, in the Chat mutants, simply the overabun- dance of axons may force some into territory that they normally would not innervate. Consistent with the idea that ChAT/ACh plays a role in restricting the development of nerve terminals to the central band of muscle, Patel and Poo (1984) demonstrated that growth cones can be guided to, and will stop growing at, a focal electrical field. When the focal electrical field is turned off, growth cones resume migration away from the focal field.…”

Influx of extracellular Ca2+ is necessary for electrotaxis inDictyostelium

“…Another possibility for the sustained elevation in [Ca 2+ ] i might involve passive influx. It is estimated that in a cell of 10-m diameter, exposed to an EF of 100 mV/mm, the cathodal side of cell membrane would depolarise by ~5 mV, whereas the membrane facing the anode hyperpolarises by the same amount (Patel and Poo, 1982;Poo, 1981). Presuming the dependence of depolarisation and/or hyperpolarisation on electric field strength is linear, an electric field of 1000 mV/mm would cause the cathodal side of cell membrane to depolarise by ~50 mV, whereas the anodal side of membrane hyperpolarise by ~50 mV.…”

Cellular mechanisms of direct-current electric field effects: galvanotaxis and metastatic disease

“…Passive influx It has been estimated that for dcEFs of 10-100 mV/mm applied to a cell 10 µm across, the cathodal side depolarizes by ∼5 mV whereas the membrane facing the anode hyperpolarizes by the same amount (Patel and Poo, 1982;Poo, 1981). This hyperpolarization could increase the electromotive force driving cations passively into the cell (Cooper and Keller, 1984).…”