Electrical stimulation induces calcium-dependent release of ngf from cultured schwann cells

Electrical Stimulation Induces Calcium-Dependent
Release of NGF From Cultured Schwann Cells
JINGHUI HUANG,1 ZHENGXU YE,1 XUEYU HU,1 LEI LU,2
AND ZHUOJING LUO1*
1Department of Spine Surgery, Institute of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
2Department of Oral Anatomy and Physiology, School of Stomatology, The Fourth Military Medical University, Xi’an, China
KEY WORDS nerve growth factor; Schwann cell; electrical stimulation; calcium; nerve injuries
ABSTRACT
Production of nerve growth factor (NGF) from Schwann cells (SCs) progressively declines in the distal stump, if axonal regeneration is staggered across the suture site after peripheral nerve injuries. This may be an important factor limiting the outcome of nerve injury repair. Thus far, extensive efforts are devoted to modulating NGF production in cultured SCs, but little has been achieved. In the present in vitro study, electrical stimulation (ES) was attempted to stimulate cultured SCs to release NGF. Our data showed that ES was capable of enhancing NGF release from cultured
SCs. An electrical field (1 Hz, 5 V/cm) caused a
4.1-fold increase in NGF release from cultured SCs. The
ES-induced NGF release is calcium dependent. Depletion of extracellular or/and intracellular calcium partially/ completely abolished the ES-induced NGF release. Further pharmacological interventions showed that ES induces calcium influx through T-type voltage-gated calcium channels and mobilizes calcium from 1, 4, 5-trisphosphate-sensitive stores and caffeine/ryanodine-sensitive stores, both of which contributed to the enhanced NGF release induced by ES. In addition, a calcium-triggered exocytosis mechanism was involved in the ES-induced NGF release from cultured
SCs. These findings show the feasibility of using ES in stimulating SCs to release NGF, which holds great potential in promoting nerve regeneration by enhancing survival and outgrowth of damaged