Cellular Physiology of Skeletal, Cardiac, and Smooth Muscle \.fLLS of each of the types df muscle to facilitate communication between takes the form of the postsynap- junction. Neuromuscularjunctions (i.e.. in cardiac and smooth muscle. In transmissiondoes not initiate contraction;it . neuromuscular cardiac important ~ Cellular Physiology of Skeletal, Cardiac, and Smooth Muscle / 9 231 Branchedstructure of cardiacmuscle ses to modulate,rather than to initiate, cardiac muscle function. In contrast to skeletal muscle, cardiac muscle contraction is triggered by electrical signals from neigh- boring cardiac musclecells. Theseelectrical impulses orig- inate in the pacemaker region of the hean, the sinoatrial node (p. 489), which spontaneouslyand periodically gen- eratesaction potentials. To facilitate direct electricalcom- munication betweencardiac muscle cells, the sarcolemma of cardiac muscle is specializedto contain gap junctions (p. 164), electrical synapsesthat couple neighboringcells (Fig. 9-1). When an action potential is initiated in one Actin ntercalated cell, current flows through the gap junctions and depolar- izes neighboring cells. If depolarizationcauses the mem- brane potential (Vm) to be more positive than threshold, self-propagatingaction potentials occur in the neighboring cells as well. Thus, the generationof an action potential is just as critical for initiating contraction in cardiacmuscle as it is in skeletalmuscle. Smooth Muscles May Contract in Responseto Either Neuromuscular Synaptic Transmission or Electrical Coupling Like skeletal muscle, smooth muscle receivessynaptic in- put from the nervous system. However, the synaptic in- Z-line put to smooth muscle differs from that to skeletalmuscle FIGURE 9- 1. Electricalcoupling of cardiac myocytes. in two ways. First, the neurons are pan of the autonomic nervous system rather than the somatic nervous system (see Chapter 15). Second, the neuron makes multiple Skeletal Muscle Contracts in Responseto contacts with a smooth muscle cell. At each contact Neuromuscular Synaptic Transmission point, the axon diameter expands to form a varicosity that contains the presynapticmachinery. The varicosity is The mature skeletal muscle cell has a single neuromuscu- in close proximity to the postsynapticmembrane of the lar junction where acetylcholine(ACh) receptorsare con- smooth muscle cell, but there is relatively little specializa- centrated(p. 209). A single muscle cell respondsto only tion of the postsynapticmembrane. Rather than the neu- a single neuron. However, a single neuronal axon may rotransmitter receptorsbeing closely clusteredat the neu- bifurcate to innervate severalindividual muscle cells. The romuscular junction, as in skeletal muscle, in smooth group of muscle cells innervated by a single neuron is muscle the receptors are spread more widely acrossthe referredto as a motor unit. postsynapticmembrane. The neuromuscularjunction is the focus of Chapter 8. The mechanismsof intercellular communicationamong Briefly, the ACh releasedby the presynapticnerve termi- smooth muscle cells are more diverse than are those of nal binds to inotropic (nicotinic) ACh receptors at the skeletal or cardiac muscle. In some organs, smooth mus- neuromuscularjunction. These receptors are nonselective cle is innervated in a manner similar to skeletalmuscle in cation channelsthat open when ACh binds to a specific that each smooth muscle cell receives synaptic input. site on the channel, and a depolarizatlen known as the However, a difference is that a smooth muscle cell may end-plate potential is produced. If this end-plate poten- receive input from more than one neuron. Moreover, tial exceedsthe threshold for activating Na+ channels,an there is little electrical coupling among these smooth action potential results. Generationof an action potential muscle cells (Le., few gap junctions). As a result, each initiates the sequenceof processesleading to contraction. smooth muscle cell may contract independently of its The ACh is rapidly inactivated by acetylcholinesterase,an neighbor. Becausethis type of smooth muscle behavesas enzyme that is manufactured by the muscle cell, and multiple, independentcells or groups of cells, it is called musclecontraction stops a few millisecondsafter neuronal multiunit smooth muscle (Fig. 9-2A). Note that the activity ceases. "multi" in "multiunit" refers to the muscle fibers' acting independentlyof one another as multiple units. Multiunit Cardiac Muscle Contracts in Responseto the smooth musclesare capableof finer control. Indeed, mul- Propagation of Electrical Signals from One tiunit smooth muscle is found in the iris and ciliary body of the eye, the piloerector musclesof the skin, and some Cardiac Cell to Another Across Gap Junctions blood vessels. Cardiac muscle cells also have chemical synapses,but the In contrast to multiunit smooth muscle, the smooth sympathetic and parasympatheticbranches of the auto- musclecells of most organshave extensive intercellular nomic nervous system (see Chapter 15) use these synap- communication in the manner of cardiac muscle cells. In ~ 232 9 I CellularPhysiology of Skeletal,Cardiac, and SmoothMuscle A B I ,11 this type of smooth muscle, gap junctions pennit electri- a smooth muscle cell capable of producing an action cal communication between neighboring cells. This com- potential-an action potential will then ensue. munication allows coordinated contraction of many cells. Action potentials are usually seenin unitary (visceral) Becausethese cells contract as a single unit, this type of smooth muscle. These action potentials typically have a smooth muscle is called unitary smooth muscle (Fig. 9- slower upstroke and longer duration (up to -100 IDS) 28). Unitary smooth muscle is the predominant smooth than do skeletalmuscle action potentials(-2 IDs). The muscle type within the walls of visceral organs such as action potential in a smooth muscle cell can be a simple the gastrointestinaltract, the uterus, and many blood ves- spike, a spike followed by a plateau,or a seriesof spikes sels. For this reason,unitary smooth muscle is often re- on top of slow wavesof VIII(Fig. 9-3A). In any case,the ferred to as visceral smooth muscle. Among unitary upstroke or depolarizing phase of the action potential smooth muscles,variation in the strength of intercellular reflects opening of voltage-gatedCa2+ channels. The in- coupling from organ to organ leads to variation in the ward Ca2+ current further depolarizes the cell and spatial extent of a single unit. For example, in the blad- thereby causesstill more voltage-gatedCa2+ channels to der, extensive coupling among cells defines large func- open. Thus, some smooth muscle cells can undergo the tional units, which allows the muscular wall of the blad- same type of regenerativedepolarization that is seen in der to contract in synchrony. On the other hand, the skeletal muscle. However, the rate of rise of the action smooth muscle cells of blood vessels couple to Conn potential in smooth muscle is lower becauseCa2+ chan- smaller, independently functioning units that are more nels open more slowly than do Na+ channelsin skeletal akin to multiunit smooth muscle. In fact, electrical cou- and cardiac muscle (p. 189). Repolarizationof the smooth pling of smooth muscle units exhibits a tissue-specific muscle cell is also relatively slow. Two explanationsmay continuum from multiunit to unitary coupling. be offered for this slower repolarization. First, voltage- gated Ca2+channels, which are responsiblefor the depo- Action Potentials of Smooth Muscles May Be larization phase of the action potential, inactivateslowly. Brief or Prolonged Second, the repolarization phase of the action potential reflects the delayed activation of voltage-gatedK+ chan- Whereasboth skeletalmuscle and cardiacmuscle produce nels and, in some cases,Ca2+ -activated K+ channels. action potentials that initiate ~ontraction, smooth muscle Some smooth muscle cells have fast, voltage-gatedNa+ cells produce a wide range of Vm variations that can channels. However, even when these channels are either initiate or modulate contraction. Action potentials present,they do not appearto be necessaryfor generating that are similar to those seen in skeletal muscle are 0b- served in unitary smooth muscle and in some multiunit an action potential. Their main role may be to allow more muscle. Uke cardiac muscle cells, some smooth muscle rapid activation of voltage-gatedCa2+ channels and thus cells exhibit prolonged action potentials that are charac- contribute to a fasterrate of depolarization. terized by a prominent plateau. Still other smooth muscle In some unitary smooth muscle, repolarization is so cells cannot generate action potentials at all. In these delayedthat the action potential contour displaysa prom- cells, Vm changesin a graded fashion (p. 173) rather than inent plateau. These plateau potentials may be several in the all-or-none manner of action potentials.The stimuli hundred milliseconds in duration, as in cardiac muscle. that produce a graded respol1K of Vm include many Plateauaction potentials occur in smooth muscle of the circulating and local humoral factors,as well as mechani- genitourinary tract, including the ureters, bladder, and cal stimuli such as stretching the cell. These graded Vm uterus.The long Vm plateauallows the entry of Ca2+to changes may be either hyperpolarizing or depolarizing; continue for a longer period and thus allows [Ca2+)1 to they sum temporally as well as spatially. If the summation remain