Question

1) Detail the complete reflex pathway involving parasympathetic signalling to the heart. Begin this at the carotid body baroreceptors.

( 2) Explain why the M2 subtype of muscarinic ACh receptors is found on the autorhythmic cells of the sinoatrial node and the M3 subtype is found on smooth muscle fibers of the bronchioles.

3) Skeletal muscle has a defined contraction period, causing the full contraction of every stimulated fiber. Part 1 - What determines the length of time during which the fiber contracts? Part 2 - What ends the contraction, so relaxation can begin? (not including the termination of the NMJ stimulation) Part 3 - Taking the previous two parts, and now adding in that the NMJ has stopped inducing depolarizations at the motor end plate, describe the events as the contraction cycle (each single twitch) ends. Part 4 - Taking the previous three parts, and now adding in that the NMJ continues to induce depolarizations at the motor end plate, explain the generation of increased muscle tension as summation occurs. 4) Using the following table for reference, explain each characteristic, especially noting the differences between fiber types within a given characteristic, and what that means to the fiber type. This of course requires you to relate the

Answer 1

1
it is important to tightly control this pressure to ensure adequate blood flow to organs throughout the body. This is accomplished by negative feedback systems incorporating pressure sensors (i.e., baroreceptors) that sense the arterial pressure. The most important arterial baroreceptors are located in the carotid sinus (at the bifurcation of external and internal carotids) and in the aortic arch (Figure 1). These receptors respond to stretching of the arterial wall so that if arterial pressure suddenly rises, the walls of these vessels passively expand, which increases the firing frequency of action potentials generated by the receptors. If arterial blood pressure suddenly falls, decreased stretch of the arterial walls leads to a decrease in receptor firing.

The carotid sinus baroreceptors are innervated by the sinus nerve of Hering, which is a branch of the glossopharyngeal nerve (IX cranial nerve). The glossopharyngeal nerve synapses in the nucleus tractus solitarius (NTS) located in the medulla of the brainstem. The aortic arch baroreceptors are innervated by the aortic nerve, which then combines with the vagus nerve (cranial nerve X) traveling to the NTS. The NTS modulates the activity of sympathetic and parasympathetic (vagal) neurons in the medulla, which in turn regulate the autonomic control of the heart and blood vessels.

2 In smooth muscle, M3 receptors mediate phosphoinositide hydrolysis and Ca2+ mobilization, whereas M2 receptors mediate an inhibition of cAMP accumulation. The inhibitory effect of the M2 receptor on cAMP levels suggests an indirect role for this receptor; namely, an inhibition of the relaxant action of cAMP-stimulating agents.
M(3) receptors interact with G(q) to trigger phosphoinositide hydrolysis, Ca(2+) mobilization and a direct contractile response. In contrast, M(2) receptors interact with G(i) and G(o) to inhibit adenylyl cyclase and Ca(2+)-activated K(+) channels and to potentiate a Ca(2+)-dependent, nonselective cation conductance. Ultimately, these mechanisms lead to the prediction that the influence of the M(2) receptor on contraction should be conditional upon mobilization of Ca(2+) by another receptor such as the M(3).competitive antagonism of a muscarinic response mediated through activation of both M(2) and M(3) receptors should resemble the profile of the directly acting receptor (i.e., the M(3)) and not that of the conditionally acting receptor (i.e., the M(2)). Using a combination of pharmacological and genetic approaches, we have identified two mechanisms for the M(2) receptor in contraction: 1) a high potency inhibition of the relaxation elicited by agents that increase cytosolic cAMP and 2) a low potency potentiation of contractions elicited by the M(3) receptor. The latter mechanism may be involved in muscarinic agonist-mediated heterologous desensitization of smooth muscle, which requires activation of both M(2) and M(3) receptors.
Receptor M2
Second messenger :cAMP,⬇️and direct coupling to K channel
Organ:heart - atrium
sinu-atrial node prejunctional at autonomic nerve endings ileum smooth muscle
Response:
reduced contractile force (negative inotropy) reduced rate (negative chronotropy) reduced NA or Ach release
Receptor:M3
Second messenger:IP3/DAGT⬆️
Organ:
smooth muscle -gut
urinary bladder trachea iris circular muscle blood vessels endothelium smooth muscle glands oxyntic cells (gastric acid)
Response:
contraction minor binding sites
release of NO and vasodilatation contraction
increased acid secretion salivation insulin release