PROPERTIES AND MODULATIONS OF BK_Ca CHANNELS IN HYPOTHALAMIC NEURONS

PROPERTIES AND MODULATIONS OF BK~a CHANNEL IN HYPOTHALAMIC NEURONS Postgraduate for MD: Wang Shuai Supervisor: Prof. Zou Fei (Department of Thermal Environmental Medicine,First Military Medical University,Guangzhou,5 10515) Abstract BK~a channels are found in a variety of regions of the central nervous system and other tissues. In recent years, a great deal of data concerning BK~a channels in nervous system has been obtained, but little is known about the properties of BK~a channels in hypothalamic neurons. In this study the inside-out and cell-attached configurations of patch-clamp techniques were used to study the physiological properties, redox modulation and NO modulation of BKca channels in hypothalamic neurons of newborn SD rats. As follows are the main results and conclusions: 1. The properties of BK~. channels in hypothalamic neurons The most fundamental response that can be measured was the fraction of channels that were open as a function of [Ca>]. BK~a channels were activated firstly at 0.05 ~t mol/L [Ca2~]~ with membrane potential of ?OmV. The P0 of the channels depended on [Ca>] and reached half-maximum at 5 i~t mol/L [Ca2~]~. Conductance of single BK~a channel was approximately -4- 171 pS with symmetrical l4OmmoI/1 K~ on both sides of excised membrane. The temporal analysis of the channels showed that the currents generated a exponential distribution of open time and a biexponential distribution of shut time in all patches. Following the increase of [Ca2~]1, the T increased, shortened and T did c2 ~ n抰 change. When [Ca2~]1 was 2 ii mol/L, Po increased e-fold for 23.4mV positive change in membrane potential and the V11. was 5.3mV. The voltage dependence of BK Ca channel was independent of [Ca>]~. These results suggested BK~a channel in hypothalamic neurons had its special characteristics and were kinetically distinguished from other cells. 2.The rectification property of BK~a channels in hypothalamic neurons Following [Ca211 increased, the outward conductance value of the channel decreased but the inward conductance value didn抰 change and rectificatus property of the channels was only observed in patches clamped at positive potential, which indicated the currents of the channel had characteristic of inward rectification. This property was regulated not only by membrane potential but also by [Ca2~]r Its reason maybe concern with Ca2~ combining with its bining site of channel protein. Mg> didn抰 influence this rectification. These high levels of [Ca>]~ which have the ability to both activate BK~a channel and thus modulate the channel抯 ability to act as rectifiers can be locally achieved in physiological situations following rapid stimulation or via various second messenger pathways. Since BK~a channels are responsible for the repolarization and afterhyperpolarization of action potential, this rectification may have something to do with the excitability and stability of neurons and allow BK~a channels in hypothalamic neurons...