9 18 Lecture 5 Ch 4 The Action Potential Ch 5 Synaptic Transmission Patch Clamp Technique channel Patch clamp technique measures current through a single ion Sensitive amplifier connected to glass pipette with tiny opening Tight contact between glass pipette and membrane achieved with suction Membrane potential controlled to study voltage dependence of current through single ion channel Current is about 1 2 pA 10 12 ampere Several orders of magnitude smaller than current measured by voltage clamping entire axon Patch clamp recording of voltage gated Na channel Properties of single voltage gated Na channels explain action potential properties o Vm depolarized increased chance of Na channel opening o Na channels open soon after depolarization thus rapid rising phase when Vm not clamped o Channels inactivate quickly thus brief action potential duration o Hyperpolarization needed to relieve inactivation explains refractory period Averaged current recorded from many single Na channels has same time course as macroscopic Na current current recorded from whole axon by traditional voltage clamp method Voltage gated potassium channels contribute to falling phase Help bring Vm back to RMP after peak of AP also called delayed rectifier channels Don t open immediately upon depolarization delay allows open Na channels to take Averaged current from many single openings has same time course as macroscopic K Vm to peak of action potential current Summary How voltage gated Na and K channels produce an action potential Na channels open soon after depolarization Inward current through Na channels Rapid Na influx brings Vm close to ENa Na channels then inactive K channels open with a delay K efflux brings Vm back to RMP close to EK The undershoot is explained by increased gK compared to rest so Vm briefly dips below RMP more positive K going out of cell inside more negative Action Potential propagates down axon Positive charges entering during AP spread away and cause membrane just ahead to depolarize to threshold resulting in an AP further down the axon Insured current doesn t die out from axon hillock down to nerve terminal AP normally propagates in one direction because membrane behind it is refractory as a result of Na channels that are inactivated Myelin reduces the leakiness of the axon and thus increases conduction velocity The further positive charge spreads ahead of the AP the faster the AP propagates down the axon 2 mechanisms evolved to increase propagation speed o 1 Increased diameter of axon reduced Ri internal resistance o 2 Myelin insulating the axon increased Rm membrane resistance Action potential conduction in myelinated axon is called salutatory conduction o The action potential occurs only at the Nodes of Ranvier o Positive charge spreads down axon but some will leak out through K channels thus reducing the amount of charge available for depolarizing the axon at further distances Myelin decreases this leak Propagation down axon is proportional to Rm Ri o Small Ri internal resistance charge goes down axon better o Large Ri internal resistance more leak current spread is passive between nodes Multiple Sclerosis MS Loss of myelin and inflammation along axons Disorder usually begins between ages 20 and 40 Symptoms depend on affected region o Vision affected wen optic nerve is involved o Muscle weakness or paralysis when motor tracts affected o Involvement of vestibular systems causes dizziness Sudden onset of symptoms lasting days to weeks then remission Cause of MS is uncertain o Autoimmune disease Infection with virus that expresses protein similar to a component of myelin membrane followed by overactive immune system attack on myelin Synaptic Transmission Chemical and Electrical Synapses Early 20th century debate whether synapses relied on electrical or chemical transfer of signals o Otto Loewi electrical stimulation of vagus nerve results in release of chemical o Electrical synapses first demonstrated in 1950s between neurons involved in later shown to be acetylcholine escape reflexes of invertebrates Lowei s experiment Electrical synapses directly transfer ionic current from one cell to another Gap junction channels consist of two connexons o Fast transmission presynaptic and postsynaptic neurons electrically coupled o Heart muscle cells connected by electrical gap junctions Electrical synapses are bidirectional o Involved in 1 rapid responses 2 synchronizing activity among populations of neurons brainstem neurons that generate breathing and hormone releasing neurons in hypothalamus 9 23 Lecture 6 Ch 5 Synaptic Transmission Most synapses are chemical synapses Neurotransmitter released from axon terminal into cleft then binds to receptors on postsynaptic membrane Axon terminal presynaptic element o Active zone site of transmitter release by exocytosis Synaptic vesicles low molecular weight neurotransmitters Secretory granules peptide neurotransmitters Synaptic cleft Postsynaptic dendrites o Postsynaptic density receptors and associated proteins Synaptic Vesicles Small clear core vesicles contain low molecular weight neurotransmitters Secretory Granules Large dense core vesicles contain peptide neurotransmitters Synaptic Arrangements Synapses are characterized by where the connection is made o A Axodendtritic synapse o B Axosomatic synapse o C Axoaxonic synapse Neuromuscular junction Synapse between neuron and muscle fiber Nervous system control of muscle contraction Motor neurons cell bodies in spinal cord axons in synapse with muscle cells fibers o Action potential in axon results in muscle cell contraction o Synaptic transmission at neuromuscular junction is relatively fast and reliable fail safe Large synapse with large number of active zones each action potential causes release of many vesicles containing acetylcholine The motor endplate region postsynaptic membrane is folded increasing surface area and number of neurotransmitter receptors for acetylcholine ACh Large suprathreshold postsynaptic potential PSP Neuromuscular junction Motor neuron action potential always leads to an action potential in muscle fiber This is an excpetion to the general rule that multiple PSPs at brain synapses must add together summate to cause an action potential Neurotransmitters can be A Amino acids GABA glutamate glycine B Amines acetylcholine dopamine epinephrine histamine norepinephrine serotonin C Peptides Neurotransmitter synthesis and storage Amino acids and Amines cytosol of terminal