The chord conductance equation describes how the transmembrane potential (Vm) is influenced by the conductance and the intracellular and extracellular concentrations of various ions, including K+ and Na+. The temporal relationship between changes in transmembrane potential and cell shortening in a single ventricular myocyte is shown in Figure 16.2. The action potentials of cardiac fibers are illustrated in Figure 16.1, with the phases and refractory periods labeled. In resting cardiac cells, the K+ conductance (gK) is about 100 times greater than the Na+ conductance (gNa), resulting in Vm being similar to the Nernst equilibrium potential for K+. Therefore, alterations in extracellular K+ concentration can significantly affect Vm, with hypokalemia causing hyperpolarization and hyperkalemia causing depolarization. On the other hand, changes in extracellular Na+ concentration do not significantly impact Vm due to the small gNa in resting cells. In certain pathological conditions, the fast responses of cardiac muscle can convert to slow responses. For instance, in coronary artery disease, an insufficient blood supply to a region of cardiac muscle can lead to an increase in interstitial fluid K+ concentration, converting the action potentials of some affected cells from fast to slow responses. The genesis of the upstroke (phase 0) of the action potential involves a sudden influx of Na+ into the myocyte due to an increase in gNa. The amplitude of the action potential is dependent on extracellular Na+ concentration, with a decrease resulting in a decrease in amplitude and a reduction to around 20 mEq/L making the cell non-excitable. The sudden depolarization of the resting membrane potential, Vm, from -90 mV to the threshold level of approximately -65 mV leads to significant changes in the cell membrane properties. Na+ enters the myocyte through specific fast voltage-activated sodium channels, which can be blocked by substances like tetrodotoxin and certain drugs used in the treatment of cardiac arrhythmias.
The dependence of Vm on conductance and the intracellular and extracellular concentrations of K+, Na+, and other ions are described by the chord conductance equation •Fig. 16.2 Temporalrelationshipbetweenthechangesintrans-membranepotential(top trace) andcellshortening(bottom trace) inasingleventricularmyocyte.Thevalueof0mVmembranepotentialisindicatedby“0.”(FromPappanoA.unpublishedrecord,1995.)0 50 mV 400 msec 7˜m •Fig. 16.1 Action Potentials of Cardiac Fibers. A, Fast-responsecardiacfibers.B, Slow-responsecardiacfibers.Thephasesoftheactionpotentialsarelabeled(seetextfordetails),asaretheeffectiverefractoryperiod(ERP)andtherelativerefractoryperiod(RRP).Notethatincomparisonwithfast-responsefibers,therestingpotential ofslowfibersislessnegative,theupstroke(phase0)oftheactionpotentialislesssteep,theamplitudeoftheactionpotentialissmaller,phase1isabsent,andtheRRPextendswellintophase4afterthefibershavefullyrepolarized.
Eq. 2.7 ). In a resting cardiac cell, K+ conductance (gK) is approximately 100 times greater than Na+ conductance (gNa). Therefore, Vm is similar to the Nernst equilibrium potential for K+ . As a result, alterations in extracellular [K+] can significantly change Vm: Hypokalemia causes hyperpolarization, and hyperkalemia causes depolarization. In contrast, because gNa is so small in the resting cell, changes in extracellular [Na+] do not significantly affect Vm.
Fastresponsesofcardiacmusclemaychangetoslowresponsesincertainpathologicalconditions.Forexample,incoronaryarterydisease,aregionofcardiacmusclemaybedeprivedofitsnormalbloodsupply.Asaresult,[K+]intheinterstitialfluidthatsurroundstheaffectedmusclecellsrisesbecauseK+ islostfromtheinadequatelyperfused(orischemic)cells.Theactionpotentialsinsomeofthesecellsmaythenbeconvertedfromfasttoslowresponses.Conversionfromafasttoaslowresponseasaresultofincreasinginterstitial[K+]isillustratedlaterin
Fig.16.13
Genesis of the Upstroke (Phase 0)
Any stimulus that abruptly depolarizes Vm to a critical value (the threshold) elicits an action potential. The characteristics of fast-response action potentials are shown in
Fig. 16.1A.
The rapid depolarization (phase 0) is related almost exclusively to the influx of Na+ into the myocyte as a result of a sudden increase in gNa. The action potential amplitude (the membrane potential change during phase 0) is dependent on extracellular [Na+]. When extracellular [Na+] is decreased, the amplitude of the action potential decreases, and when it is reduced from its normal value of approximately 140 mEq/L to approximately 20 mEq/L, the cell is no longer excitable.
When the resting membrane potential, Vm, is suddenly depolarized from −90 mV to the threshold level of approximately −65 mV, the cell membrane properties change dramatically. Na+ enters the myocyte through specific fast voltage-activated sodium channels that exist in the membrane (see
Fig. 5.7). These channels can be blocked by the puffer fish toxin tetrodotoxin. In addition, many drugs used to treat certain cardiac rhythm disturbances (cardiac arrhythmias) act by blocking these fast sodium channels.