Lecture 4.1: Membranes and Receptors - Electrical Excitability PDF

Membranes and Receptors Electrical Excitability The action potential and its properties Session 4 - Lecture 4.1  Aims of the lecture By the end of this lecture the student should be able to: ❖ Identify the properties of the action potential (AP) and its io...

Membranes and Receptors Electrical Excitability The action potential and its properties Session 4 - Lecture 4.1  Aims of the lecture By the end of this lecture the student should be able to: ❖ Identify the properties of the action potential (AP) and its ionic basis. ❖ Outline the changes in membrane ionic permeability. ❖ Describe the basis of the all-or-none law and refractoriness. ❖ Demonstrate some molecular properties of ion channels. ❖ Apply these facts of the action of local an aesthetics. ❖ Identify the properties of the action potential (AP) and its ionic basis. ❖ Outline the changes in membrane ionic permeability. ❖ Describe the basis of the all-or-none law and refractoriness. Action potential (AP): ❖ Change in voltage across membrane. ❖ Depends on ionic gradients and relative permeability. ❖ Action potentials are nerve impulses and are not graded potentials. ❖ They are changes in membrane potential. Once they begin, all parts of an excitable membrane will be affected. ❖ Action potentials are propagated along axon surfaces -Membrane potential is the voltage difference across a cell's membrane(cytoplasm is more negative than outside the cell -  Action potential (AP): 1. A stimulus from a sensory cell or another neuron causes the target cell to depolarize to-ward the threshold potential 2. If the threshold of excitation is reached, all Na+ channels open and the membrane depolarizes. 3. At the peak action potential, K+ channels open and K+ begins to leave the cell. At the same time, Na+ channels close 4. The membrane becomes hyperpolarized as K+ ions continue to leave the cell. 5. The hyperpolarized membrane is in a refractory period and cannot fire 6. The K+ channels close and the Na+/K+ transporter restores the resting potential. Action potentials are generated by an increase in permeability to Na+, bringing the membrane close to the Na+ equilibrium potential, The sodium hypothesis of the action potential. The action potential should be greatly influenced by the concentration of sodium ions in the external fluid Effects of changes of membrane potential on sodium and potassium currents.  Intracellular recording of Action potentials in axons, skeletal muscle, SA node and cardiac ventricular muscle  Cardiomyocyte Action Potential: One Individual Cell 1- Depolarization/Contraction. 2- Plateau/Ensures Full Flux of Blood From Chamber Contracting 3- Repolarization/Relaxation  Action potential in Contractile myocytes ✓ Because of the plateau phase, cardiac muscle stays contracted longer than skeletal muscle. This is necessary for expulsion of blood from the heart chambers. The absolute refractory period is also much longer- 250 msec compared to 1 msec in skeletal. This long refractory period is to make sure the muscle has relaxed before it can respond to a new stimulus and is essential in preventing summation and tetanus, which would stop the heart from beating. What happens during the upstroke (depolarization) of the AP ?  Repolarization of action potentials is a two-stage process involving the inactivation of Na+ channels and the activation of K+ channels. Note……… that Na,K pump is NOT involved in the repolarization of the action potential. After an action potential, most of the Na+ channels have been inactivated. Before they can open again, they need time to recover. They can only do this when the membrane potential has returned to its resting level.  Recovery after an action potential ARP= absolute refractory period RRP= relative refractory period ARP - nearly all Na+ channels are in the inactivated state RRP - Na+ channels are recovering from in activation, the excitability returns towards normal as the number of channels in the inactivated state decreases  The molecular nature of voltage-gated channels has been determined ❖The Voltage-gated ion channels are a class of trans membrane proteins that form ion channels that are activated by changes in the electrical membrane potential near the channel. ❖ membrane potential alters the conformation of the channel proteins, regulating their opening and closing ❖ The opening and closing of the channels are triggered by changing ion concentration, and hence charge gradient, between the sides of the cell membrane  ❖ There are two major types of ion channel: voltage gated, and Ligand gated ❖ Voltage gated ion channels open in response to voltage (i.e. when the cell gets depolarized) where as. ligand gated channels open in response to a ligand (some chemical signal) binding to them.· ❖ The Voltage-gated ion channels are responsible for ✓ maintaining neuronal homeostasis and function ✓ secretion, ✓ endocytosis, ✓ muscle contraction, ✓ synaptic transmission, ✓ ciliary control, ✓ fertilization, etc. Na+ and Ca2+channels are similar, their main pore forming subunit is one peptide consisting of 4 homologous repeats. Each repeat consists of 6 transmembrane spanning domains with one of these domains being able to sense the voltage field across the membrane.