CHEMICAL TRANSDUCTION & MODULATION OF CHANNEL CURRENTS

化学信号在细胞之间不断流动

The incessant flow of chemical signals between and among the individual neural elements of the brain is widely acknowledged to be an essential determinant of higher neural function. Therefore the physiological mechanisms which underlie the ability of primary olfactory receptor neurons to detect, transduce and process chemical signals must provide a good model for these processes elsewhere in the brain. Individual olfactory receptor neurons respond to multiple chemical stimuli and differ dramatically in the particular array of effective odorants and in the relative amounts of each required to elicit a significant change in action potential production. In receptor neurons, most receptor sites, second messenger systems and single current channels are thought to be integral plasma membrane proteins. Thus, the complexity seen in olfactory receptor neurons can be ascribed to differences in the kind, number, distribution, activation and interaction among these individual proteins. Activation of receptor sites is presumed to stimulate or modulate in some way, perhaps through a second messenger mechanism, various ionic currents which flow through the integral membrane channels. These brief individual currents, in concert, ultimately result in sufficient transmembrane current flow to generate a propagated action potential. In these experiments fragments of insect olfactory receptor neuron dendrites will be reconstituted in phospholipid bilayers on the tips of patch electrodes in order to explore the biophysics of olfactory transduction, signal amplification and current flow. The questions to be asked include: 1) Does an individual odor interact with more than one kind of receptor site? 2) Are there different kinds of receptor sites on single olfactory receptor neurons? 3) If there are, how many kinds are there and how do they differ in their individual binding properties? 4) Does the activation of one type of receptor site influence the activation of another? 5) How are these receptor sites coupled to the activation of single channel currents? 6) Do effective odors modulate single channel currents directly, or indirectly through a second messenger system? 7) If second messenger systems are involved, how are they modulated and regulated? 8) Are particular types of receptor sites always associated with a particular type of channel or second messenger system? 9) How many different types of individual channel currents are there? 10) How do channels vary in their ionic requirements and voltage dependence? Answers to these questions will aid in our understanding of brain function.