Università degli Studi di Perugia


Study-unit Code
Luigi Catacuzzeno
  • Luigi Catacuzzeno
  • 47 ore - Luigi Catacuzzeno
Course Regulation
Coorte 2021
Learning activities
Discipline del settore biomedico
Type of study-unit
Obbligatorio (Required)
Type of learning activities
Attività formativa monodisciplinare
Language of instruction
Ion channel: structural determinants of gating and selectivity. Na and K channels relevant in the action potential generation. Electric behavior of a plasmamembrane. Computer simulations and ionic basis of an action potential. Molecular basis of sinaptic transmission. 
Reference texts
material prepared by the teacher
Educational objectives
Good knowledge of behaviour and function of ion channels; experience in the simulation of cellular excitability
In order to understand the points treated during the course, student should have the following preliminary knowledge:1) Principles of general physiology. Particularly important is the membrane excitability and the different types of membrane transport2) Citology of neuronal and skeletal muscle cells3) Principloe of biochemistry, with particutal enphasis on the structure of proteins and phospholipids. Theory of fluid mosaic of biological membranes. 
Teaching methods
Frontal lessons
Learning verification modality
Written partial tests and final oral exam.
Written tests are three in number, each consisting of three questions requiling a few line of text to answer. The oral exam consists of nine questions performed over all the program.
Extended program
Structure of ion channels: hydropathy plots and predictionof transmembrane topology; cridtallographic analysis. Use of the patch-clamp tecnique in the study of ion channels: whole-cell, inside-out e outside-out configurations. Mechanisms of gating: state transition theory. Voltage-dependent gating: relationship between the open probability and membrane voltage, Boltzmann equation and its derivation. Molecular basis of voltage sensing. Activation kinetics of ion channels: ensamble average and macroscopic currents. Kinetic schemes for the description of ion channel behaviour. Definition of kinetic constants. Differential equetion describing the behaviour of ion channel gating. Inactivation and its molecular bases: experiments with intracellular proteases and with deletion of the intracellular protein domains in Shaker K channels. Kinetic description of voltage-gated Na and K channels. Ligand-gated ion channels: relationship open probability - agonost cncentration and Hill equation. Molecular basis of calcium sensitivity of BK channels. Na channels: structure and diversification of voltage-gated Na channels; epithelial Na channels. Ca channels: structure and diversification of voltage-gated Ca channels; store-operated Ca channels. K channels: structure and diversification of voltage-gated K channels; calcium-dependent K channels; background K channels; inward rectifier K channels. Cl channels. Structure and diverdity of ligand-gated channels: nicotinic receptors; GABA and glycine receptors; ionotropic serotonin receptors; glutamate receptors; ATP receptors; aquaporins, gap junctions. 
Phases of the migraine attack: increase of the migraine triggers; activation of trigeminovascular neurons; neurogenic inflamation; transmition of the nociceptive information to second order neurons; central sensitization; familial hemiplegic migraine (FHM) and the involvment of voltage-gated Ca channels. Functional consequences of FHM mutations. Analysis of papers clarifying the role of ion channels in migraine. 

Fundamentals of the use of xpp software for the resolution of first order differential equations; simulation of the kinetic behaviour of voltage-gated Na and K channels. Ion channel control of the membrane potential. Similarities between the plasmamembrane and the electrical behavior of the RC circuit. Differential equation for the dynamics of membrane voltage; simulation of an excitable membrane containing voltage-gated Na and K channels; role of Ca-activated K channels and voltage-gated Ca channels in shaping the action potential. 
Chemical and electrical synapses; structural and molecular properties of chimica synapses; sequence of events involved in synaptic transmission; depolarization and calcium influx into the presynaptic membrane: dynamics of presynaptic calcium and calcium concentration microdomains. The vesicle cycle: quantal neurotransmitter release and its statistical properties; diffusion and disappearance of the neurotransmitter. Short and long term synaptic plasticity; postsynaptic potentials; spatial and temporal summation; presynaptic receptors and control of neurotransmitter release; retrograde transmission. Long term depression and potentiation; pahse of induction; phase of expression.
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