Rats In Excitable Cells, Ion Channels And Calcium Regulation

As the most important second messenger, Ca2+ controls many physiological events, such as neurotransmitter release and muscle contraction. While cytoplastic Ca2+ concentration is usually kept below 0.1-0.2 (M, it will rise to function in intracellular signaling after excitation, with Ca2+ passing through Ca2+-permeable ion channels in plasma membrane and Ca2+-release channels in endoplasmic reticulum/sarcoplasmic reticulum (ER/SR). In pancreatic ??cells, Ca2+ couples excitation (high glucose) and insulin secretion, through voltage-dependent Ca2+ channels (VDCCs). In neurons and cardiac myocytes, when action potentials depolarize the plasma membrane, Ca2+ influx through VDCCs is a key point in transmitter release and muscle contraction. In order to widely understand Ca2+-dependent physiological events,we studied Ca2+ stores in rat pancreatic ??cells, and pacemaker channels in rat DRG neurons and rat ventricular myocytes. The main results obtained are listed below:We found ER Ca2+ store is functionally separate in pancreatic ??cells, which may be divided into IP3 and Ryanodine common Ca2+ store, and only IP3-sensitive store. Thiopentone can induce insulin secretion due to IP3-sensitive calcium release.Using combined whole-cell recording and fluorescence Ca2+ imaging, we found Ca2+ can permeate hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, and contribute 0.47%-0.60% of total HCN4 and HCN2 induced currents, respectively. In DRG neurons, Ih channel is also permeable to Ca2+, which contributes to activity-evoked neuronal secretion.In rat ventricular myocyte, we found Ca2+, when entering the cell through If channels, can induce muscle contraction at negative membrane potentials and shorten the action potential duration.Taken together, our results demonstrated that Ca2+ rise by non-classical pathway also plays some important roles in physiological events. This is important for modulation of cell secretion and muscle contraction under normal conditions, and may represent a previously undiscovered mechanism in certain pathophysiological conditions.