Comparative Vertebrate
Physiology ’03
Web-Human
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 ________________
Name
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)