9 Faris Haddad Dania Alkouz Mohammad-Khatatbeh
Revision of previous ideas I. The Action potential stages are mainly controlled by Na+ and K+ channels II. These channels can be either pumps (chemical gated) or voltage- gated channels III. Pumps are mainly used in the maintenance of RMP IV. Voltage-gated channels are inaction mainly in depolarization and repolarization V. Cardiac tissues can be grouped into 2 types, differentiated by the different type of action potential they operate with (to be studied later). VI. Action potential is initiated by reaching a threshold potential using chemical gates or existing currents in the membrane Refractory Period Action potential is initiated by sodium voltage-gate channels which go through 3 states during the cycle: Closed and capable of opening: during RMP and polarisation before threshold, since these channels are electromotive sensitive they do not open before the potential threshold is reached, but they do have the capacity to open when it is reached to allow action potential to occur Open: once the potential threshold is reached, which is around -50 to -70 millivolts, the voltage-gate channels have their activation gates open in a conformation change allowing Na+ huge permeability (from 500x to 5000x under RMP) in the depolarisation stage. Actually the change of permeability is so great that the membrane's potential gets neutralised and even becomes positive in a matter of a few 10000ths of a second. 1 Page
Closed and not capable of opening (inactive):once maximum positive potential is reached, the inactive gate of the channels become inactive (plug themselves) to prevent any further gaining of charge or experiencing action potential during the repolarization period, this period is called refractory period. This state of the channel can be reversed by polarisation beyond the potential threshold and the hyperpolarisation that succeeds repolarisation contributes to the deinactivation of the channels; the greater the negative potential the greater the deinactivation rate The refractory period is a stage in action potential when the membrane resists restimulation by not responding to any small stimuli that initiated the process in the beginning. It is divided into 2 periods : The absolute refractory period (ARP): when there is an over-whelming concentration of inactive Na+ voltage-gated channels (closed and not capable to open ) that respond to no stimuli, no matter how strong they are. Meaning action potential not possible. note:- Dr khatatbeh said that Na+ voltage-gated channels are open in ARP, as in the handout. But in the book, inactive (closed and not capable to open). The relative refractory period (RRP): when the membrane is recovering and coming back to RMP, during this period only very strong stimuli can elicit a response from the membrane. Action potential can theoretically reignite so Na+ voltage-gate channels are closed and capable to open, but our bodies usually experience sub-threshold currents. 2 Page
A clear, relative time frame for each period wasn't mentioned above because there is no clear time frame, different textbooks and data references disagree on when each start and end, so what has been mentioned will do. This also leads to the conclusion; the magnitude of the action potential is practically fixed, its frequency isn t. The greater the magnitude of Na+ concentration the grater the stronger the stimulus which means action potential may happen during relative -RP which means the intensity of the a neural signal isn t expressed by the membrane potential s strength, but by frequency. * The greater the negative potential of a membrane the easier it'll be for it to be excited because a negative potential causates to a greater concentration of "closed but capable for opening" channels, and so greater frequency of action potential. This bit of information is also the logical conclusion to the question why do different cells have different RMP?". Neurons RMP: -90 mv Smooth muscle cells RMP: -40 mv 3 Page
These numbers make sense when you consider the functions of each cell. Neurons can recover from action potential quickly so they can start the next cycle quickly. Even the difference between threshold potential and RMP for each of those cells gets smaller the more negative RMP. Pacemaker Conductive tissues: a tissue with a higher permeability to sodium, that greater influx means that the threshold is reached faster, accelerating depolarization, these tissues use calcium channels to accelerate depolarization since Ca ions are double the charge of Na ions, but the channels are slow to open thus they are called slow channels while Na ion channels are called fast channels. This tissue is exclusive to cardiac muscles, which means the heart s action potential is not dependent upon neural impulses. These tissues also have higher concentration of K channels to help in repolarisation. Now what function does all this serve in the heart? The Na voltage gates being fast channels will depolarise the membranes of the tissues first, the Ca channels can maintain the new positive charge of the membrane after the now deactivated Na channels; prolonging the depolarisation stage. This Plateau phase insures that the contractions happen in the same direction everywhere. This also leads to more and more K channels becoming active, ready for repolarisation after the deactivation of the Ca channels. This is all regulated by one part of the Heart called pacemaker (SA node). This action potential s refractory period lasts longer so the heart doesn t start contracting again while it s contracting. 4 Page
In these cases where both Ca and Na contribute to action potential, these ions can have effects on each other s channels. For example; a deficit in Ca will cause the Na voltage gated channels to become easily excitable, this can cause the respiratory muscle cells for example to discharge with no stimulus in a phenomena called muscle tetany which can be lethal sometimes Neurons Neurons are the cells responsible for the transmission of commands to organs to maintain homeostasis, simply put they generate and transmit action potential. Action potential gets transmitted in pulses; during action potential the membrane is +ve compared to RMP. In motor neurons for example the axon is so long that different parts of the membrane have different potentials, which generates a current starting from the cell body. The signal gets transmitted from one neuron to the next through 2 types of synapses: Chemical synapses: where the presynaptic cell transmits neurotransmitters over the synaptic cleft to the postsynaptic cell s receptors which can stimulate the channels to start another action potential. Electrical synapses: where the neurons are attached together with gap junctions that allow the current to flow. 5 Page
Now being electrical impulses in a very fluid and conductive environment, the action potential impulses are insulated from the extracellular environment of the axon by myelin sheaths (a lipid based white substance), and those little gaps in the sheath are not a hindrance they help the spreading of the action potential and are called nodes of Ranvier. Myelin is really effective in helping action potential conduct through myelinated axons that the impulse seams to leap from one node to the next, so they called it saltatory conduction (from Latin saltare, to leap ) Myelin is secreted by a type of secondary supportive cell that falls into a group called neuroglia, or "glial cells" that have many vital functions including: 1. Myelin secretion: Oligodendrocytes and Schwann cells 2. Phagocytises to destroy dead neurons or invading microbes: Microglial cells 3. Assistance in ion regulation: Astrocytes 4. Anchoring of the neuron to capillaries 6 Page