NEUROMUSCULAR AND SYNAPTIC TRANSMISSION D. C. Mikulecky Professor of Physiology http://views.vcu.edu/~mikuleck/ TWO TYPES OF SYNAPSE • ELECTRICAL • CHEMICAL ELECTRICAL GAP JUNCTION: PROVIDES PATH FOR IONS TO FLOW FROM ONE CELL TO ANOTHER CELL 1 CELL 2 TYPES OF CHEMICAL SYNAPSES • DISCRETE • DIFFUSE DISCRETE SYNAPSES DIFFUSE SYNAPSES CHEMICAL: THE SYNAPSE INCOMING NERVE POST SYNAPTIC NERVE SPACE EVENTS IN CELLULAR COMMUNICATION INPUT SIGNAL (CHEMICAL,MECHANICAL, PHOTO, ELECTRICAL) RECEPTOR TRANSDUCER EFFECTOR ENZYMES,GENOME,CONTRACTILE FILAMENTS, SECRETORY GRANULES RESPONSE (OUTPUT) SECRETION CONTRACTION/RELAXATION DIVISION PHAGOCYTOSIS HOW ARE WE WIRED?CONNECTIONS BETWEEN NERVE CELLS CELL BODY AXON AXON TERMINALS AXON HILLOCK DENDRITES THE NATURE OF CHEMICAL TRANSMISSION BETWEEN NERVES • PRESYNAPTIC EVENTS • POSTSYNAPTIC EVENTS • IN THE SPACE PRESYNAPTIC EVENTS • THE ALL OR NONE ACTION POTENTIAL TRIGGERS THE RELEASE OF CHEMICAL TRANSMITTER INCOMING ACTION POTENTIAL • DEPOLARIZES • TRIGGERS CALCIUM CHANNELS • CALCIUM ENTERS THE CELL THE SYNAPSE INCOMING ACTION POTENTIAL CALCIUM CHANNEL ••• SYNAPTIC VESSICLES ••• ••• ••• RECEPTOR ••• ••• ••• ••• ••• ENZYME ION CHANNEL THE SYNAPSE: INCOMING ACTION POTENTAL INCOMING ACTION POTENTIAL CALCIUM CHANNEL ••• SYNAPTIC VESSICLES ••• ••• ••• RECEPTOR ••• ••• ••• ••• ••• ENZYME ION CHANNEL CALCIUM INFLUX • CAUSES VESSICLES TO BE RELEASED • VESSICLES MIGRATE TO MEMBRANE • EXOCYTOSIS • NEUROTRANSMITTER ENTERS SPACE THE SYNAPSE: CALCIUM CHANNELS OPEN INCOMING ACTION POTENTIAL CALCIUM CHANNEL ••• SYNAPTIC VESSICLES ••• ••• ••• RECEPTOR ••• ••• ••• ••• ••• ENZYME ION CHANNEL THE SYNAPSE: NEUROTRANSMITTER ENTERS SPACE CALCIUM CHANNEL ••• SYNAPTIC VESSICLES ••• ••• ••• ••• ••• ••• RECEPTOR ••• ••• ENZYME ION CHANNEL POST SYNAPTIC EVENTS • IONOTROPIC (LIGAND GATED) CHANNELS • VOLTAGE GATED CHANNELS • ELECTROPHYSIOLOGICAL PRINCIPLES IONOTROPIC CHANNELS • BIND NEUROTRANSMITTER • OPEN CHANNEL • HYPER OR DE-POLARIZATION THE SYNAPSE:NEUROTRANSMITTER BINDS TO POSTSYNAPTIC RECEPTOR CALCIUM CHANNEL ••• SYNAPTIC VESSICLES ••• RECEPTOR ••• ••• ••• ••• ••• ••• ••• ••• ENZYME ION CHANNEL HOW ARE WE WIRED?CONNECTIONS BETWEEN NERVE CELLS CELL BODY AXON AXON TERMINALS AXON HILLOCK DENDRITES POSTSYNAPTIC POTENTIALS IPSP RESTING POTENTIAL TIME EPSP SPATIAL SUMMATION SIMULTANEOUS INPUT FROM TWO SYNAPSES: ABOVE THRESHOLD THRESHOLD TIME SPATIAL SUMMATION SIMULTANEOUS INPUT FROM TWO SYNAPSES: ABOVE THRESHOLD THRESHOLD TIME TEMPORAL SUMMATION TOO FAR APART IN TIME: NO SUMMATION TIME TEMPORAL SUMMATION CLOSER IN TIME: SUMMATION BUT BELOW THRESHOLD THRESHOLD TIME THE GOLDMAN-HODGKIN-KATZ (GHK) EQUATION [Ko] + [Nao] Vm = 60 LOG -------------------------[Ki] + [Nai] IS THE RATIO OF SODIUM TO POTASSIUM PERMEABILITY TEMPORAL SUMMATION STILL CLOSER IN TIME: ABOVE THRESHOLD THRESHOLD TIME EPSP-IPSP CANCELLATION HOW EXCITATION OCCURS-THE ROLE OF DEPOLARIZATION AND HYPERPOLARIZATION • SUMMATION CAN DEPOLARIZE THE CELL BEYOND THRESHOLD • HYPERPOLARIZATION BLOCKS NEURO TRANSMITTERS • • • • • ACETYL CHOLINE DOPAMINE NOREPINEPHRINE EPINEPHRINE SEROTONIN • • • • HISTAMINE GLYCINE GLUTAMINE GAMMAAMINOBUTYRIC ACID (GABA) IN THE SPACE • ENZYME “CHEWS UP” LIGAND • MASS ACTION CAUSES LIGAND TO DISSOCIATE FROM RECEPTOR THE SYNAPSE CALCIUM CHANNEL ••• SYNAPTIC VESSICLES ••• RECEPTOR ••• ••• ••• ••• ••• ••• ••• ENZYME ION CHANNEL THE SYNAPSE CALCIUM CHANNEL ••• SYNAPTIC VESSICLES ••• ••• ••• RECEPTOR ••• ••• ••• ••• ••• ENZYME ION CHANNEL