Biophysics of excitable cells H.Gaub / SS 2007 BPZ§4.1 1 Axons are specialized for the conduction of an electrical impulse called an action potential H.Gaub / SS 2007 BPZ§4.1 2 Specialized regions of neurons carry out different functions H.Gaub / SS 2007 BPZ§4.1 3 Experimental techniques are conceptually simple H.Gaub / SS 2007 BPZ§4.1 4 H.Gaub / SS 2007 BPZ§4.1 5 Cell-Semiconductor-Hybrids: Neuron on the Chip More: Fromherz MPI Martinsried H.Gaub / SS 2007 BPZ§4.1 6 Cell-Semiconductor-Hybrids: Neuron on the Chip H.Gaub / SS 2007 BPZ§4.1 7 Synapses are specialized sites where neurons communicate with other cells H.Gaub / SS 2007 BPZ§4.1 8 Multiple exitatory and inhibitory synaptic contacts allow complex neuronal interconnects H.Gaub / SS 2007 BPZ§4.1 9 Neurons are organized into circuits The knee-jerk reflex arc in the human. H.Gaub / SS 2007 BPZ§4.1 10 A schematic of the vertebrate nervous system H.Gaub / SS 2007 BPZ§4.1 11 Membrane depolarizations spread passively only short distances H.Gaub / SS 2007 BPZ§4.1 12 The electrical activity of neurons results from the opening and closing of specific ion-channels proteins in the neuron plasma membrane H.Gaub / SS 2007 BPZ§4.1 13 Voltage-gated cation channels generate action potentials H.Gaub / SS 2007 BPZ§4.1 14 The structure and function of the voltage-gated Na+ channel H.Gaub / SS 2007 BPZ§4.1 15 Action potentials are propagated unidirectionally without diminution Movements of only a few Na+ and K+ ions generate the action potential H.Gaub / SS 2007 BPZ§4.1 16 Myelination increases the velocity of impulse conduction H.Gaub / SS 2007 BPZ§4.1 17 Formation and structure of a myelin sheath in the peripheral nervous system H.Gaub / SS 2007 BPZ§4.1 18 Each region of myelin formed by an individual glial cell is separated from the next region by an unmyelinated area called the node of Ranvier H.Gaub / SS 2007 BPZ§4.1 19 Action potentials travel rapidly from one node to the next H.Gaub / SS 2007 BPZ§4.1 20 Patch clamps permit measurement of ion movements through single channels H.Gaub / SS 2007 BPZ§4.1 21 Different patch clamping configurations H.Gaub / SS 2007 BPZ§4.1 22 Current flux through individual voltage-gated channels determined by patch clamping of muscle cells H.Gaub / SS 2007 BPZ§4.1 23 The oocyte expression assay can be used to determine if a protein is an ion channel H.Gaub / SS 2007 BPZ§4.1 24 Voltage-gated K+ channels have four subunits each containing six transmembrane helices H.Gaub / SS 2007 BPZ§4.1 25 All five subunits in the nicotinic acetylcholine receptor contribute to the ion channel H.Gaub / SS 2007 BPZ§4.1 26 P segments form the ion-selectivity filter H.Gaub / SS 2007 BPZ§4.1 27 All pore-forming ion channels are similar in structure H.Gaub / SS 2007 BPZ§4.1 28 Acetylcholine and other transmitters can activate multiple receptors Acetylcholine is released by motor neurons at neuromuscular junctions H.Gaub / SS 2007 BPZ§4.1 29 Neurotransmitters are small molecules that transmit impulses at chemical synapses H.Gaub / SS 2007 BPZ§4.1 30 Influx of Ca2+ triggers release of neurotransmitters Synaptic vesicles can be filled, exocytosed, and recycled within a minute H.Gaub / SS 2007 BPZ§4.1 31 Synaptic-vesicle and plasma-membrane proteins important for vesicle docking and fusion H.Gaub / SS 2007 BPZ§4.1 32 Chemical synapses can be excitatory or inhibitory H.Gaub / SS 2007 BPZ§4.1 33 Ligand-gated receptor ion channels function at fast synapses H.Gaub / SS 2007 BPZ§4.1 34 G protein-coupled receptors function at slow synapses H.Gaub / SS 2007 BPZ§4.1 35 Transmitter-mediated signaling is terminated by several mechanisms • Following release of a neurotransmitter or neuropeptide, it must be removed or destroyed to prevent continued stimulation of the post-synaptic cell • To end the signaling, the transmitter may – diffuse away from the synaptic cleft – be taken up by the pre-synaptic neuron – be enzymatically degraded • Signaling by acetylcholine and neuropeptides is terminated by enzymatic degradation • Signaling by most classic neurotransmitters is terminated by uptake H.Gaub / SS 2007 BPZ§4.1 36 Impulses transmitted across chemical synapses can be amplified and computed H.Gaub / SS 2007 BPZ§4.1 37 Opening of acetylcholine-gated cation channels leads to muscle contraction H.Gaub / SS 2007 BPZ§4.1 38 Cardiac muscarinic acetylcholine receptors activate a G protein that opens an ion channel Catecholamine receptors also induce changes in second-messenger levels that affect ion-channel activity H.Gaub / SS 2007 BPZ§4.1 39 A serotonin receptor indirectly modulates K+ channel function by activating adenylate cyclase H.Gaub / SS 2007 BPZ§4.1 40 Membrane disks in the outer segments of rod cells contain rhodopsin, a lightsensitive protein H.Gaub / SS 2007 BPZ§4.1 41 Absorption of a photon triggers isomerization of retinal and activation of opsin H.Gaub / SS 2007 BPZ§4.1 42 Cyclic GMP is a key transducing molecule in rod cells H.Gaub / SS 2007 BPZ§4.1 43 A thousand different G protein-coupled receptors detect odors H.Gaub / SS 2007 BPZ§4.1 44 Impulse transmission across electric synapses is nearly instantaneous H.Gaub / SS 2007 BPZ§4.1 45 Comparison of action potential transmission across electric and chemical synapses H.Gaub / SS 2007 BPZ§4.1 46 Learning and memory • Learning is the process by which animals modify their behavior as a result of experience or acquisition of information about the environment • Memory is the process by which this information is stored and retrieved – Long term memory involves the formation or elimination of certain synapses – Short-term memory involves changes in the release and function of neurotransmitters at specific synapses H.Gaub / SS 2007 BPZ§4.1 47 Study of the gill withdrawal reflex of Aplysia has provided insight into shortterm learning processes H.Gaub / SS 2007 BPZ§4.1 This simple behavior exhibits the most elementary forms of learning familiar in vertebrates: habituation, sensitization, and classical conditioning 48 Facilitator neurons mediate sensitization of Aplysia withdrawal reflex Individuals were restrained in small aquariums in a manner that the gill was exposed. A tactile stimulus was administered to the siphon and elicited the gill and siphon withdrawal reflex. A photocell was placed under the gill to record amplitude and duration of the response elicited by the stimulus. Habituation was observed when the stimulus was delivered repeatedly to the siphon. Stimulus every 90 seconds resulted in a rapidly declined response. By delivering an electric shock to the tail the response was rapidly restored, dishabituation occurred. Sensitization was observed when a strong stimulus was administered to the tail, this enhanced a completely rested reflex in Aplysia californica. H.Gaub / SS 2007 BPZ§4.1 49 Coincidence detectors participate in classical conditioning and sensitization H.Gaub / SS 2007 BPZ§4.1 50