TARGET REGULATION OF VOLTAGE-GATED CALCIUM CHANNEL EXPRESSION IN NODOSE GANGLION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ion channel expression is an important aspect of neuronal development. Over the last 5 years we have been interested in understanding what factors regulate ion channel expression in developing neurons. Using the chick nodose ganglion (NG) as a model, we have obtained clear evidence that voltage-gated, calcium channel expression is regulated by target innervation and cell-cell interactions. Whole cell patch clamp recordings reveal that low voltage-activated (LVA) calcium channels are not present in immature E7 NG neurons. Treatment of E7 NG neurons with a heart extract for 48 hr induces the expression of LVA channels. Our current model indicates that expression of LVA calcium channels in NG neurons is regulated by interaction with a heart-derived factor via a Ca2+-dependent mechanism. This proposal is designed to investigate some important aspects of our working model by pursuing the following specific aims: 1) To investigate whether a cardiac muscle tissue-derived factor mediates the stimulatory effect of HEx on LVA Ca2+ channel expression; 2) To investigate the nature of the HEx-stimulating factor that upregulates LVA Ca2+ channel expression; and 3) To investigate whether the stimulating effect of HEx on LVA channel expression requires protein synthesis and signaling via a Ca2+-dependent mechanism.