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.