Contents

General Cellular Morphology Cardiac Muscle Cells Force Production

Cardiac Muscle Electrical Activity

Summary

Sources

1. GENERAL CELLULAR MORPHOLOGY

All human cells can be considered biological machines surrounded by a membrane bilayer (plasma membrane). The average thickness or diameter of a nonmuscle cell is approx 10-20 p,m. The encapsulating membrane is studded with various receptors for hormones or other circulating biochemicals (Fig. 1). The plasma membrane also contains a number of ion-specific pumps and channels. The interior of each cell contains enzymes and organelles specialized to support a wide array of biological functions. Key organelles include the nucleus (contains the genetic blueprint for cellular function), mitochondria (converts various energy sources to adenosine triphosphate, a general energy currency), and the endoplasmic reticulum and the Golgi apparatus (supports protein synthesis) (Fig. 1). Muscle cells are similar in that they use some of these common organelles, but different in that they are specialized to generate force.

2. CARDIAC MUSCLE CELLS

A comparison of an idealized cell to a cardiac muscle cell reveals several distinct specializations (Figs. 1 and 2). The shapes of mammalian cardiac fibers do not conform to a simple geometry, so measurement of their size is not straightforward, and a single measurement of length or width would be inadequate or often misleading. Yet, in general they tend to have a shorter width (10-40 p,m) and a longer dimension (~50-200 p,m) along the force generation axis. The individual cells sometimes possess branches (Fig. 2). Importantly, most of the inter-

From: Handbook of Cardiac Anatomy, Physiology, and Devices Edited by: P. A. Iaizzo © Humana Press Inc., Totowa, NJ

nal volume of myocytes is devoted to a cytoskeletal lattice of contractile proteins with a liquid crystalline order that gives rise to a striated appearance under the microscope (Fig. 3). As with other cell types, the membrane bilayer contains a collection of ion channels and pumps and receptor proteins. In addition, the membranes of cardiac muscle cells contain unique proteins designed to connect cardiac myocytes to one another as both mechanical and electrical partners.

The arrangement of the contractile proteins in cardiac muscle cells is similar to that found in skeletal muscle. Yet, skeletal muscle cells tend to be much larger than cardiac cells; they can be centimeters long, with diameters ranging from 20 to 100 p,m.

For comparison, the action of skeletal muscles can be voluntary or reflexively controlled (postural) and is thus under direct control of the nervous system. on the other hand, the action of cardiac muscle is involuntary and rhythmic (~80 contractions/min). This rate can be modulated by nervous system input, but it does not initiate cardiac contractions. Both muscle types are activated via a calcium-dependent process involving troponin (Tn), a protein that acts as a thin filament-based calcium sensor.

2.1. Myocyte Internal Structure

A closer examination of cardiac myocytes reveals several important structural features. First, similar to skeletal muscle, the contractile proteins are organized into sarcomeres (Fig. 4), which are the contractile functional units, bordered on each end by a protein matrix known as the Z line. The Z lines are primarily composed of the protein a-actinin. Within each sarcomere, there is an interdigitating lattice of thick and thin protein fila-

Fig. 1. General cellular morphology. This "typical cell" is a fluid-filled membrane vesicle. The membrane contains receptors and ion channels that act as "gatekeeper" molecules controlling the response of the cell to the external environment. The interior of the cell contains specialized organelles integral to the cell's function.

Fig. 2. Elements of cardiac cell morphology. The contractile proteins form a lattice that gives cardiac cells their distinctive appearance. The high concentration of contractile proteins relegates the nucleus, mitochondria, and other organelles to the periphery of the cell.

Fig. 1. General cellular morphology. This "typical cell" is a fluid-filled membrane vesicle. The membrane contains receptors and ion channels that act as "gatekeeper" molecules controlling the response of the cell to the external environment. The interior of the cell contains specialized organelles integral to the cell's function.

Fig. 3. Cardiac cell landmarks. This diagram points out key features of the sarcomeric structure within contractile myocardial cells. On the left side, key features of the sarcomeric organization of the contractile proteins are listed. The remaining labels highlight other key elements in cardiac cell structure. Note the intimate relationship between the contractile cells and the coronary blood vessel.

Fig. 2. Elements of cardiac cell morphology. The contractile proteins form a lattice that gives cardiac cells their distinctive appearance. The high concentration of contractile proteins relegates the nucleus, mitochondria, and other organelles to the periphery of the cell.

ments. The thin filaments extend from the Z line for about 1 ^m toward the center of the sarcomere and are polymeric assemblies of globular subunits of the protein actin. The thick filaments are bipolar assemblies of the protein myosin.

Myosin molecules have long a-helical tails that form the backbone of the thick filaments, and each has two globular head domains. The bipolar nature of these filaments is such that the heads extend from each end of the filaments with a bare zone in the center (Fig. 4). Myosin heads possess the ability to form crossbridges with the actin thin filaments and, upon binding actin, act as the molecular motors responsible for muscle contraction. The region of the sarcomere in which the myosin fila-

Fig. 3. Cardiac cell landmarks. This diagram points out key features of the sarcomeric structure within contractile myocardial cells. On the left side, key features of the sarcomeric organization of the contractile proteins are listed. The remaining labels highlight other key elements in cardiac cell structure. Note the intimate relationship between the contractile cells and the coronary blood vessel.

ments reside is known as the A band (Fig. 4). The area between A bands of adjacent sarcomeres is known as the I band; this area is bisected by the Z lines and is traversed by actin thin filaments that extend from the Z line toward the center of both sarcomeres (Fig. 4).

2.2. Tropomyosin and Troponin

As noted, the thin filaments are formed from the actin backbone, but they also carry the regulatory proteins tropomyosin (Tm) and Tn (Fig. 5). Tropomyosin is a double-stranded, a-helical, coiled-coil protein that spans seven actin monomers. In contrast, troponin is a globular protein complex with three sub-units: (1) TnC, a calcium-binding subunit; (2) Tnl, a subunit that inhibits muscle contraction; and (3) TnT, a subunit that connects the troponin complex to tropomyosin and actin. Tro-pomyosin molecules are aligned end to end around the helical coil of the thin filament with one Tn complex attached to each Tm molecule.

In relaxed muscle, tropomyosin binds to actin in such a way that it impedes the binding of the myosin heads to actin-bind-ing sites. However, on muscle activation and the subsequent increase in myoplasmic calcium concentrations, free calcium binds to troponin, inducing a conformational change that is

Fig. 4. Protein components of the contractile machinery. Each cardiac myocyte contains bundles of myofibrils that run the length of the cell. Myofibrils are a serial array of contractile units called sarcomeres. Within the sarcomeres, actin and myosin are arranged in filaments with interaction that is the molecular basis of muscle contraction.

Fig. 4. Protein components of the contractile machinery. Each cardiac myocyte contains bundles of myofibrils that run the length of the cell. Myofibrils are a serial array of contractile units called sarcomeres. Within the sarcomeres, actin and myosin are arranged in filaments with interaction that is the molecular basis of muscle contraction.

Aclin

Fig. 5. Calcium regulation of contraction. The regulatory proteins troponin and tropomyosin regulate contraction by blocking the myosin-binding sites on actin in the absence of calcium. Calcium binding to troponin induces tropomyosin movement, allowing actomyosin force generation.

Aclin

Fig. 5. Calcium regulation of contraction. The regulatory proteins troponin and tropomyosin regulate contraction by blocking the myosin-binding sites on actin in the absence of calcium. Calcium binding to troponin induces tropomyosin movement, allowing actomyosin force generation.

transmitted to tropomyosin; it shifts its position on the actin thin filament to reveal the site on actin required for strong myosin binding. Myosin can then bind to the thin filament in a manner conducive to force production. This association of tropomyosin with troponin over seven actin monomers represents the de facto regulatory unit along the thin filament.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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