Drexel University College of Medicine

Intracellular Ca²⁺ is essential for cellular functions such as neurotransmitter release.  Cytoplasmic Ca²⁺ levels are regulated by calcium influx through calcium permeable channels on the cell membrane.  Ca²⁺ -release activated Ca²⁺ (CRAC) entry, also termed store-operated Ca²⁺ entry (SOCE), is a major mechanism for Ca²⁺ influx in non-excitable cells.  In contrast to the well known function of SOC channels in non-excitable cells, the functional significance of SOCE in the CNS remains elusive.  Recently, it has been shown that calcium influx through SOC channels play a critical role in synaptic transmission.  Our preliminary data suggests that SOC channels are expressed in spinal cord dorsal horn and DRG neurons. 

Studies in our laboratory aim to identify the molecular components of SOC channels in two main regions of the pain neuraxis (primary sensory neurons, dorsal horn neurons), and investigate the role of SOC channels in synaptic plasticity and their signaling pathways in modulatino of nociception.  We employ a variety of approaches, including behavioral tests, patch clamp electrophysiology, calcium imaging, biochemical and molecular analysis to address the following questions:

• Which molecular identities mediate SOC entry in DRG and dorsal horn neurons?
• Are SOC channels involved in synaptic transmission in spinal cord?
•  What are the signaling pathways involved in SOC channel activation?
• Are SOC channels involved in pain plasticity?

These studies will help us elucidate the role of SOC channels in the pain pathway.  We hope to identify molecular targets to develop new treatments for chronic pain associated with injury and disease.