• •

Vm

2 ms

t

− 80 mV

•

Vm

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Vm

FIGURE 1.2

A nerve action potential and its first and second time derivatives (derivatives not to scale).

1.4Muscle Action Potentials

1.4.1Introduction

An important bioelectric signal that has diagnostic significance for many neuromuscular diseases is the electromyogram (EMG), which can be recorded from the skin surface with electrodes identical to those used for electrocardiography, although in some cases, the electrodes have smaller areas than those used for ECG (<1 mm2). To record from single motor units (SMUs) or even individual muscle fibers (several of which comprise an SMU), needle electrodes that pierce the skin into the body of a superficial muscle can also be used. (This semi-invasive method obviously requires

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sterile technique.) EMG recording is used to diagnose some causes of muscle weakness or paralysis, muscle or motor problems such as tremor or twitching, motor nerve damage from injury or osteoarthritis, and pathologies affecting motor end plates.

1.4.2The Origin of EMGs

There are several types of muscle in the body, e.g., striated, cardiac, and smooth. Striated muscle in mammals can be further subdivided into fast and slow muscles (Guyton, 1991). Fast muscles are used for fast movements; they include the two gastrocnemii, laryngeal muscles, extraocular muscles, etc. Slow muscles are used for postural control against gravity and include the soleus; abdominal, back, and neck muscles; etc. EMG recording is generally carried out on both types of skeletal muscles. It can also be done on less superficial muscles such as the extraocular muscles that move the eyeballs, the eyelid muscles, and the muscles that work the larynx.

A particular striated muscle is innervated by a group of motor neurons that have origin at a certain level in the spinal cord. In the spinal cord, motor neurons receive excitatory and inhibitory inputs from motor control neurons from the CNS, as well as excitatory and inhibitory inputs from local feedback neurons from muscle spindles (responding to muscle length, x, and dx/dt), Golgi tendon organs (responding to muscle tension), and Renshaw feedback cells (Northrop, 1999; Guyton, 1991). Individual motor neuron axons controlling the contraction of a particular striated muscle innervate small groups of muscle fibers in the muscle called a single motor unit (SMU). Many SMUs comprise the entire muscle. The synaptic connections between the terminal branches of a single motor neuron axon and its SMU fibers are called motor end plates (MEPs). MEPs are chemical synapses in which the neurotransmitter, acetylcholine (ACh), is released presynaptically and then diffuses across the synaptic cleft or gap to ACh receptors on the subsynaptic membrane.

When a motor neuron action potential arrives at an MEP, it triggers the exocytosis or emptying of about 300 presynaptic vesicles containing ACh. (Approximately 3 ∞ 105 vesicles are in the terminals of a single MEP; each vesicle is about 40 nm in diameter.) Some 107 to 5 ∞ 108 molecules of ACh are needed to trigger a muscle action potential (Katz, 1966). The ACh diffuses across the 20 to 30 nm synaptic cleft in approximately 0.5 MS; here some ACh molecules combine with receptor sites on the protein subunits forming the subsynaptic, ion-gating channels. Five high molecular weight protein subunits form each ion channel. ACh binding to the protein subunits triggers a dilation of the channel to approximately 0.65 nm. The dilated channels allow Na+ ions to pass inward; however, Cl– is repelled by the fixed negative charges on the mouth of the channel.

Thus, the subsynaptic membrane is depolarized by the inward JNa (i.e., its transmembrane potential goes positive from the approximately −85 mV resting potential), triggering a muscle action potential. The local subsynaptic

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Nerve AP at MEP

FIGURE 1.3

A typical single-fiber muscle action potential recorded intracellularly at the motor end plate and 2 mm along the fiber.

transmembrane potential can go to as much as +50 mV, forming an end plate potential (EPP) spike fused to the muscle action potential it triggers with a duration of approximately 8 MS, much longer than a nerve action potential. The ACh in the cleft and bound to the receptors is rapidly broken down (hydrolized) by the enzyme cholinesterase resident in the cleft, and its molecular components are recycled. A small amount of ACh also escapes the cleft by diffusion and is hydrolyzed as well.

Once the postsynaptic membrane under the MEP depolarizes in a superthreshold end plate potential spike, a muscle action potential is generated that propagates along the surface membrane of the muscle fiber, the sarcolemma. It is the muscle action potential that triggers muscle fiber contraction and force generation. Typical muscle action potentials, recorded intracellularly at the MEP and at a point 2 mm from the initiating MEP, are shown in Figure 1.3. A skeletal muscle fiber action potential propagates at 3 to 5 m/sec; its duration is 2 to 15 msec, depending on the muscle, and it swings from a resting value of approximately −85 mV to a peak of approximately +30 mV. At the skin surface, it appears as a triphasic spike of 20to 2000-μV peak amplitude (Guyton, 1991).

To ensure that all of the deep contractile apparatus in the center of the muscle fiber is stimulated to contract at the same time and with equal strength, many transverse, radially directed tubules penetrate the center of

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8 Analysis and Application of Analog Electronic Circuits

the fiber along its length. These T-tubules are open to the extracellular fluid space, as is the surface of the fiber, and they are connected to the surface membrane at both ends. The T-tubules conduct the muscle action potential into the interior of the fiber in many locations along its length.

Running longitudinally around the outsides of the contractile myofibrils that make up the fiber are networks of tubules called the sarcoplasmic reticulum (SR). Note that the terminal cisternae of the SR butt against the membrane of the T-tubes. When the muscle action potential penetrates along the T-tubes, the depolarization triggers the cisternae to release calcium ions into the space surrounding the myofibrils’ contractile proteins. The Ca++ binds to the protein troponin C, which triggers contraction by the actin and myosin proteins. (The molecular biophysics of the actual contraction process will not be discussed here.)

A synchronous stimulation of all of the motor neurons innervating a muscle produces what is called a muscle twitch; i.e., the tension initially falls a slight amount, rises abruptly, and then falls more slowly to zero again. Sustained muscle contraction is caused by a steady (average) rate of (asynchronous) motoneuron firing. When the firing ceases, the muscle relaxes.

Muscle relaxation is actually an active process. Calcium ion pumps located in the membranes of the SR longitudinal tubules actively transfer Ca++ from outside the tubules to inside the SR system. The lack of Ca++ in proximity to troponin C allows relaxation to occur. In resting muscle, the concentration, [Ca++], is about 10−7 M in the myofibrillar fluid (Guyton, 1991). In a twitch, [Ca++] rises to approximately 2 ∞ 10−5 M and, in a tetanic stimulation, [Ca++] is about 2 ∞ 10−4 M. The Ca++ released by a single motor nerve impulse is taken up by the SR pumps to restore the resting [Ca++] level in about 50 msec.

Just as in the case of the sodium pumps in nerve cell membrane, the muscles’ Ca++ pumps require metabolic energy to operate; adenosine triphosphate (ATP) is cleaved to the diphosphate to release the energy needed to drive the Ca++ pumps. The pumps can concentrate the Ca++ to approximately 10−3 M inside the SR. Inside the SR tubules and cisternae, the Ca++ is stored in readily available ionic form, and as a protein chelate, bound to a protein, calsequestrin.

So far, the events associated with a single muscle fiber have been described. As noted earlier, small groups of fibers innervated by a single motoneuron fiber are called a single motor unit (SMU). In muscles used for fine actions, such as those operating the fingers or tongue, fewer muscle fibers, or, equivalently, more motoneuron fibers per total number of muscle fibers, are in a motor unit. For example, the laryngeal muscles used for speech have only two or three fibers per SMU, while large muscles used for gross motions, such as the gastrocnemius, can have several hundred fibers per SMU (Guyton, 1991). To make fine movements, only a few motoneurons fire out of the total number innervating the muscle and these do not fire synchronously. Their firing phase is made random in order to produce smooth contraction. At maximum tetanic stimulation, the mean frequency on the motoneurons is

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