9723676 Schneider Nerve cells communicate with each other by the release of chemical messengers or neurotransmitters, which then act on neighboring cells to complete transmission of the message. The release of the chemical neuro- transmitter is regulated by a brief rise and decay in cell calcium in the nerve endings or terminals. Whatever regulates the calcium levels in the nerve terminals will in turn regulate the rate, amount and duration of release of the chemical neurotransmitter. The objective of the present project is to clarify the mechanisms regulating the calcium signals for neurotransmitter release using a model nerve cell system known as adrenal chromaffin cells. Chromaffin cells derive from the interior of the adrenal gland and like nerves, secrete their neurohormones, adrenaline and noradrenaline, in response to a rise in cell calcium. While the cellular mechanisms regulating the rise in cell calcium are well understood, those regulating the buffering and decay of the calcium signal for secretion are not well defined. Such mechanisms are important since they in turn will regulate the strength and duration of communication between nerve cells. The present project will test a novel mechanism for regulating calcium signal decay which uses a sodium- dependent calcium transport protein to remove calcium from the cell. Such transport proteins are known as sodium- calcium exchangers and may exist in several different forms in different cellular compartments. The role and nature of the sodium-calcium exchange proteins in calcium signal decay will be determined. The project should result in an improved understanding of the cellular mechanisms regulating the calcium signal for neurotransmitter release and the identitiy of the calcium transport proteins involved in cellular calcium clearance and signal decay.
