Periodic oscillations in membrane potential can occur as a result of changes in the activity of Na+,K+-ATPase in the sarcolemma. These oscillations in membrane potential can trigger multiple action potentials in the cell. Alternatively the contractile activity of smooth muscle may not be associated with generation of action potentials or even a change in membrane potential. In many smooth muscles the resting membrane potential is sufficiently depolarized (−60 to −40 mV) that a small decrease in membrane potential can significantly inhibit influx of Ca++ through voltage-gated Ca++ channels in the sarcolemma. By decreasing Ca++ influx, the force developed by smooth muscle decreases. Such a graded response to slight changes in the resting membrane potential is common in multiunit smooth muscles that maintain constant tension (e.g., vascular smooth muscle).
Contraction of smooth muscle in response to an agent that does not produce a change in membrane potential is termed pharmacomechanical coupling and typically reflects the ability of the agent to increase the level of the intracellular second messenger InsP3. Other agents result in a decrease in tension, also without a change in membrane potential. These agents typically increase levels of the intracellular second messengers cyclic guanosine monophosphate (cGMP) or cyclic adenosine monophosphate (cAMP). The molecular mechanisms by which InsP3, cGMP, cAMP, and Ca++ alter the contractile force of smooth muscle are presented later.
Phosphorylation of a myosin light chain is required for the interaction of myosin with actin, and although Ca++dependent phosphorylation plays a key role in this process, the level of myosin phosphorylation (and hence the degree of contraction) is dependent on the relative activities of both myosin light-chain kinase (MLCK, which promotes phosphorylation) and myosin phosphatase (MP, which promotes dephosphorylation). Several agonists/hormones increase the level of myosin light-chain phosphorylation by simultaneously activating MLCK through an increase in intracellular [Ca++] and inhibiting MP through a signaling cascade involving the monomeric G protein RhoA and its effector Rho kinase (ROK). Moreover, hyperactivity of this RhoA/ROK signaling cascade has been implicated in various pathological conditions such as hypertension and vasospasm (discussed later).
Innervation of Smooth Muscle
Neural regulation of smooth muscle contraction depends on the type of innervation and neurotransmitters released, the proximity of the nerves to the muscle cells, and the •Fig. 14.5 Relationshipsbetweenmembranepotential(Em)andgenerationofforce(F)indifferenttypesofsmoothmuscle.A,Actionpotentialsmaybegeneratedandleadtoatwitchorlargersummedmechanicalresponses.Actionpotentialsarecharacteristicofsingle-unitsmoothmuscles(manyviscera).Gapjunctionspermitthespreadofactionpotentialsthroughoutthetissue.B,Rhythmicactivityproducedbyslowwavesthattriggeractionpotentials.Thecontractionsaregenerallyassociatedwithaburstofactionpotentials.Slowoscillationsinmembranepotentialusuallyreflecttheactivityofelectrogenicpumpsinthecellmembrane.C,Toniccontractileactivitymayberelatedtothevalueofthemembranepotentialintheabsenceofactionpotentials.GradedchangesinEmarecommoninmultiunitsmoothmuscles(e.g.,vascular),whereactionpotentialsarenotgeneratedandpropagatedfromcelltocell.D,Pharmacomechanicalcoupling;changesinforceproducedbytheadditionorremoval(arrows) ofdrugsorhormonesthathavenosignificanteffectonmembranepotential.
type and distribution of the neurotransmitter receptors on the muscle cell membranes (