Comparative Vertebrate Physiology ’03
Cardiac & Smooth Muscle – Lab and Lecture Supplement
General Introduction (and lecture supplement/reprise)
Via the lecture and text we have been discussing how the basic ‘invention’ of the use of the interaction of actin and myosin to generate shortening and/or force has been adapted in various manners to meet the particular needs of a situation. These adaptations range from the molecular/cellular level (skeletal, cardiac and smooth muscle) on through the functional muscle level (force velocity characteristics of flight vs. digging muscles) and finally the gross organizational level (e.g. the placement of fulcrum points to achieve power vs. speed) out of the same basic muscle contractile mechanism. In addition we have seen further adaptations to meet highly specific needs (mollusk catch muscle, insect flight muscle, etc.).
This lab focuses on the adaptation of the contractile mechanism to differing tasks via the creation of specific muscle types (skeletal, smooth and cardiac) to perform specific types of tasks. As we have devoted a great deal of our lecture time to the skeletal muscle model, this lab focuses most directly on aspects of cardiac and smooth muscle.
Cardiac muscle has its main task the development of a moderately rapid, somewhat forceful contraction that has to be reliable enough to repeat itself throughout the lifetime of the heart and also to be continuously graded (to increase/ decrease rate and force) to meet current needs.
Smooth muscle typically lines hollow structures and adjusts their diameter (e.g. airway conductance, bladder emptying, gastric propulsion of food, blood vessel diameter). As such it does not have to have a rapid or forceful contraction but does need to be continuously adjustable according to the need of the situation (e.g. desired vessel resistance).
The need for continuous activity has resulted in both types of muscle possessing self-firing capability independent of any nervous stimulation (compare with vertebrate skeletal muscle motor units). This is achieved by inward depolarizing currents (Iin) that are capable of spontaneously firing the tissue action potential. The need for fine graded adjustment in both types of muscle has led to their control by the autonomic nervous system in a push/pull manner with the sympathetic and parasympathetic tone (action potential frequency) determining the final level of operation.
Recall that cardiac muscle is self-pacing and yet excited by sympathetic neurohumors (e.g. NE, E) and inhibited by parasympathetic neurotransmitters (Ach). Smooth muscle (e.g. vascular smooth muscle) is similarly responsive to autonomic neurohumors (NE stimulates constriction and is some rare cases Ach dilates).
Each of these actions occurs, of course, via the mediation of neurotransmitter receptors. Thus in the sympathetic system one type of adrenergic (=adrenalin) receptor , a beta adrenergic receptor, when bound by NE stimulates both rate and force of the heart. A second type of adrenergic receptor, the alpha receptor, mediates the NE-induced contraction of vascular smooth muscle. Cholinergic effects at the heart (decrease rate and force) are mediated via muscarinic Ach receptors . Since these effects are each receptor specific it becomes possible to selectively block one or another of these actions via the natural evolution of or the pharmacological synthesis of receptor specific blockers (e.g. alpha blockers, beta blockers, etc.)
Finally it is worth noting that not all receptor mechanisms achieve their effects by opening linked ion channels which is the main mechanism stressed in lecture. Rather (see web site) a second class of mechanism, a slower but longer acting(an potentially more powerful) GTP second messenger system is sometimes involved. Thus while Ach slows cardiac muscle via an ion channel -linked mechanism (the receptor binding activates the opening of linked K+ channels which by opening tend to hyperpolarize the membrane making it more resistant to reaching threshold and firing), the NE beta receptor stimulation of the heart works via a GTP second messenger system in which (see web site) NE binding activates GTP which in turn acts to activate the closure of cardiac pacemaker cell K” channels. The lessening of the inward K current at ‘rest’ results in the depolarizing forces (Ina & Ica, both inward) gaining the upper hand and causing the fiber to approach threshold and fire. Thus beta receptors, when bound, increase cardiac rate.
In this lab you will briefly explore the simultaneous coordinated action of the adjustment of sympathetic stimulation on both cardiac and vascular smooth muscle and the effect of administering pharmacological receptor specific blocking agents.
Recall that vertebrate cardiovascular regulation centers around blood pressure (AP) homeostasis and that short term pressure regulation is the responsibility of the nervous system baroreflexes. The coordinated response often involves both cardiac muscle control (adjust rate, force) and (vascular) smooth muscle control (dilate or constrict)
Indeed when one adjusts one’s postural position this perturbs blood pressure and elicits a ‘tilt’ reflex that attempts to restore pressure to normal. When rising to a standing (=upright) position from lying down (prone) blood pools in the lower body, lowering pressure in the neck (baroreceptor) region and the head (i.e. brain). The tilt reflex acts to raise central pressure back toward normal by coordinating both a sympathetic acceleration of cardiac rate and force and a smooth muscle targeted vasoconstriction in the legs. Thus the tilt reflex allows us to observe simultaneously adjustments in both cardiac and smooth muscle tone by the autonomic nervous system.
The design of the experiment is
- to first lie the model down (UP = -1.0) and allow it to stabilize and
- then elicit the tilt reflex by directing it to right itself (UP = 1.0).
During this process we monitor cardiac muscle rate (PULSE) and force (stroke volume ,SV) and smooth muscle vascular tone via vascular conductance (COND) and resistance (total peripheral resistance, TPR) thus giving us a profile of sympathetic activity (SYMPNA) in regulating each parameter to meet the current needs (stabilizing arterial pressure (AP) near normal values.
This design is then repeated after an alpha adrenergic blocker (phenoxybenzamine, PHOXY) is administered allowing one to conclude from the data pattern which of the two processes, the cardiac or smooth muscle, is alpha receptor mediated.
The steps in performing the simulation are as follows:
1) Set up columns to read out cardiac and smooth muscle responses
Set table columns as follows:
SYMPNA, PULSE, SV, AP, COND, TPR (look these up in Help if you have a question about them or their units)
2) Lie the model down prone – set UP = -1.0
3) Run out 15 min. of control data at 1 min intervals – (note well that web-HUMAN’s response to the prone position is quite abnormal; while variables do change in this direction on lying down a reverse tilt reflex normally minimizes these effects; recall that no model has any more response in it than the machinery built in mathematically!)
4) Bring the model to an upright position (UP =1.0) to elicit the tilt reflex and follow it for 5 min. with 1 min. between printouts. (note also that tilt responses occur rapidly so that HUMAN’s 1 min. minimum interval is hardly ideal). Print out your results. If you wish graph (use percent) PULSE and COND as indicators of the two responses.
5) Reset the model up to prepare for the alpha blocker run (<Start Over> and repeat the steps 1-3).
6) Look up phenoxybenzamine in the Pharmacy (Charts...., Pharmacy) and note the maximum dose.
7) In the main web-HUMAN screen administer PHOXY at a maximum dose , set the model upright (step 4 above) and run for 5 min. with 1 min. between printouts. Print out your results. If you wish graph (use percent) PULSE and COND as indicators of the two responses.
8) Analysis – see next page
Note: Retain these pages; add them to your lecture notes.
Web-Human Control of Cardiac and (Vascular) Smooth Muscle ________________
From the print outs (and, if applicable, graphs) compare the responses with (see 7) and without (see 4 above) the alpha blocker and reach a conclusion as to which muscle type (cardiac or vascular smooth) the blocker works on and briefly support your reasoning from the data.
(Please hand in only this page; retain the others with your lecture notes)