Biological membranes and bioelectric phenomena Biological membrane • It is not possible to understand the origin of resting and action membrane voltage (potential) without knowledge of structure and properties of biological membrane. • In principle, it is an electrically non-conducting thin bilayer (6-8 nm) of phospholipid molecules. There are also built-in macromolecules of proteins with various functions. Considering electrical phenomena, two kinds of proteins are the most important: the ion channels and pumps. In both cases these are components of transport mechanisms allowing transport of ions through the non-conducting phospholipid membrane. Bioelectric phenomena • The electric signal play a key role in controlling of all vitally important organs. They ensure fast transmission of information in the organism. They propagate through nerve fibres and muscle cells where they trigger a chain of events resulting in muscle contraction. They take a part in basic function mechanisms of sensory and other body organs. • On cellular level, they originate in membrane systems, and their propagation is accompanied by production of electromagnetic field in the ambient medium. • Recording of electrical or magnetic signals from the body surface is fundamental in many important clinical diagnostic methods. Structure of the membrane Channels • The basic mechanism of the ion exchange between internal and external medium of the cell are the membrane channels. They are protein molecules but, contrary to the pumps with stable binding sites for the transmitted ions, they form water-permeable pores in the membrane. Opening and closing of the channels (gating) is performed in several ways. Besides the electrical gating we can encounter gating controlled by other stimuli in some channels (chemical binding of substances, mechanical tension etc.). • The passage of ions through the whole channel cannot be considered to be free diffusion because most channels are characterised by certain selectivity in ion permeability. Sodium, potassium, calcium or chloride channels are distinguished. • In this kind of ion transport there is no need of energy delivery. Electrical and chemical gating Ion transport systems • Many ion transport systems were discovered in cell membranes. One of them, denoted as sodium-potassium pump (Na/K pump) has an extraordinary importance for production of membrane voltage. It removes Na-ions from the cell and interchanges them with K-ions. Thus, the concentrations of these ions in the intracellular and extracellular medium (they are denoted as [Na+], [K+] and distinguished by indexes i, e) are different. We can write: Principle of the sodium-potassium pump Function of biological membranes • They form the interface between the cells and also between cell compartments. • They keep constant chemical composition inside bounded areas by selective transport mechanisms. • They are medium for fast biochemical turnover done by enzyme systems. • Their specific structure and selective ion permeability is a basis of bioelectric phenomena. Action potential • The concept of action potential denotes a fast change of the resting membrane potential caused by over-threshold stimulus which propagates into the adjacent areas of the membrane. • This potential change is connected with abrupt changes in sodium and potassium ion channels permeability. • The action potential can be evoked by electrical or chemical stimuli which cause local decrease of the resting membrane potential. Mechanism of action potential triggering Action potential • Changes in the distribution of ions caused by action potential are balanced with activity of ion pumps (active transport). • The action potential belongs among phenomena denoted as „all or nothing“ response. Such response is always of the same size. Increasing intensity of the over-threshold stimulus thus manifests itself not as increased intensity of the action potential but as an increase in action potential frequency (rate). Propagation of AP and local currents Examples of action potentials Definition • Synapse is a specific connection between two neurons or between neurons an other target cells (e.g. muscle cells), which makes possible transfer of action potentials. We distinguish: • Electrical synapses (gap junctions) – close connections of two cells by means of ion channels. They enable a fast two-way transfer of action potentials. • Chemical synapses – more frequent, specific structures, they enable one-way transfer of action potentials. Synaptické mediátory (neurotransmitery) • The most frequent mediators (neurotransmitters) of excitation synapses are acetylcholine (in neuromuscular end plates and CNS) and glutamic acid (in CNS). Both compounds act as gating ligands mainly for sodium channels. Influx of sodium ions inside the cell evokes a membrane potential change in positive sense – towards a depolarisation of the membrane (excitation postsynaptic potential). • Gamma-amino butyric acid (GABA) is a neurotransmitter of inhibitory synapses in brain. It acts as a gating ligand of chloride channels. Chloride ions enter the cell and evoke so a membrane potential change in negative sense – membrane hyperpolarization results (inhibitory postsynaptic potential) Summary • Electric phenomena on biological membranes play a key role in functioning of excitatory tissues (nerves, muscles) • Resting membrane potential (correctly: membrane voltage) is a result of a non-equal distribution of ions on both sides of the membrane. • It is maintained by two basic mechanisms: selective permeable ion channels and by transport systems – both these systems have protein character • Changes of membrane voltage after excitation are denoted as action potentials • Membrane undergoes two phases after excitation: depolarization – connected with influx of sodium iions into the cell - and subsequent repolarization – connected with efflux of potassium ions from the cell • In the refractory period, the membrane is either fully or partly insensitive to stimulation • Synapse is a connection of two cells which enables transmission of action potentials