 Hello and welcome to Physiology Open. For this video, have a look at this question. In this question, there are two statements. First statement is an assertion and the second statement is the reason for the first statement. Now you have to choose from the following five options. You can pause the screen and think about the answer. By the end of the video, we will see whether you got the right answer or not. OK, so to solve the question, we need to know three things. First thing is pre-potential or pacemaker potential. Then what are G protein coupled receptors and how anis affects both the above. We will see each of them one by one. So just a quick recap of pacemaker potential. We have discussed it in another video also. This graph is showing pacemaker potential. This is the potential of the auto-rhythmic cells that is SA node and AV node. X axis represents time in milliseconds while Y axis represents voltage in millivolt. The lowest voltage is known as maximum diastolic depolarization. HCN channels and T type calcium channels are responsible for phase four. This phase four is responsible for automaticity of nodal cells. Opening of L type calcium channels and entry of calcium into the cells is responsible for phase zero and opening of potassium channels and efflux of potassium from the cells is responsible for phase three. Remember, all these channels are present on the membrane of nodal cells. Now let us see what are G protein coupled receptors. On the membrane of the nodal cells are also present receptors for neurotransmitters which are released from sympathetic and parasympathetic nerves. Sympathetic nerve releases noradrenaline and the receptor for noradrenaline on the membrane is beta one receptor. On the other hand, parasympathetic nerve releases acetylcholine and the receptor is mascarinic receptor of M2 type. Both these receptors are coupled with certain proteins known as G proteins. These alpha beta gamma which you see are subunits of G proteins. This G alpha which you see is of two types. G alpha S where S stands for the stimulatory and G alpha I where I stands for inhibitory. The G protein associated with beta one receptor is S type that is a stimulatory type and that with M receptor is of inhibitory type. So the term stimulatory and inhibitory obviously means that they may stimulate or inhibit something respectively. Actually, there is a protein adenyl cyclase attached on the membrane. GS activates this adenyl cyclase leading to formation of more CAMP while GI inhibits it. All right, now let us combine the information and see how autonomic nervous system affects the heart rate. See when there is stimulation of sympathetic system then released noradrenaline binds with this beta one receptor. Due to this G alpha S gets activated and it causes activation of adenyl cyclase which in turn leads to formation of CAMP. These HCN channels which are responsible for pre-potential, their opening and closing is affected by the concentration of CAMP inside the cells. The name of this HCN channel is hyperpolarization gated cyclic nucleotides. So the CAMP is a cyclic nucleotide. When CAMP increases the probability of opening of these channels increases. So in short, sympathetic activation leads to more opening of HCN channels causing more entry of sodium inside the cells leading to faster change in the potential towards threshold. That means there is a change in this slope of the pre-potential which becomes steeper and due to this SNO generates more number of impulses in the same time. Hence it increases heart rate. On the other hand, parasympathetic activation has an opposite effect. Acetylcholine released from vagus causes activation of GI type of proteins which inhibits adenyl cyclase leading to decreased production of CAMP. Does it leads to decreased opening of HCN channels and also T type calcium channels? So obviously less sodium ions and less calcium ions will be able to enter the cells leading to decrease in the slope of the potential. So what it will cause? It will result in the decrease in the number of impulses generated and hence decreased heart rate. Now parasympathetic activation has one more effect. It delays the closure of these potassium channels which are responsible for phase 3. So more potassium moves out which leads to hyperpolarization. That is more negative maximum diastolic potential. See, since it is more negative now the voltage change required to reach to the threshold is more. So it will take more time. In summary, sympathetic activation increases heart rate by increasing the probability of opening of HCN channels and hence increasing the slope of pre-potential. While parasympathetics leads to more negative maximum diastolic depolarization and decreased slope of the pre-potential. So with this, let us now come back to our original question. Assertion says parasympathetic stimulation decreases the heart rate by decreasing the slope of the pre-potential. Yes, this is a correct statement, right? Reason statement says, Stimulatory G proteins coupled to mascarinic receptors increase the opening of HCN channels. Well, this is a wrong statement since mascarinic receptors are associated with inhibitory G proteins which decrease the opening of HCN channels. So our answer is third option. A is true but R is false. Okay, thanks for watching the video and don't forget to subscribe to the channel Physiology Open.