Ventricular myocytes

Figure 4.5 Influence of oxidant stress on action potentials recorded In an isolated rabbit ventricular myocyte, (a) Control action potential, (b) Action potential recorded 3 min after exposure to oxidant stress induced by the photoactivation of rose bengal (50 nu). (c) Spontaneous and repetitive action potential discharges induced 6.5 min after exposure to rose bengal. Action potentials were recorded via a 2.5 MQ suction electrode and a current-clamp amplifier. The cell was stimulated at 0.1 Hz with a 2 ms suprathreshold current pulse and, when the cell showed automaticity (after 6 min), stimulation was stopped. Redrawn from Matsuura and Shattock (1991b).

Figure 4.7 Changes in intraceiiuiar calcium in cultured rat ventricular myocytes exposed to oxidant stress. Calcium was measured using the fluorescent probe Fura>2. The ratio of the Fura-2 fluorescence measured at 340 and 380 nm excitation is shown and this is proportional to the intracellular calcium concentration. The fast-speed traces shown (note the 3.5 s time-scale) were recorded after various durations of oxidant stress. Myocytes under control conditions (before t = 0) show spontaneous calcium transients. These transients decreased in frequency with oxidant stress until cells failed to show spontaneous activity but continued to maintain a low intracellular calcium.

The possible role of cellular glutathione status in the controlling sarcolemmal protein activity has been addressed by studying the effect of GSH, GSSG and several other thiol and disulphide compounds on Na/K ATPase activity using (1) an isolated bovine ventricular Na/K ATPase preparation (2) crude sarcolemmal preparations (biochemical studies) (c) Langendorff-perfiised isolated hearts (cytochemical studies) and (4) isolated ventricular myocytes (electrophysiologjcal studies). 

This technique has been used to investigate the effect of the photoactivation of rose bengal on /wa/K in isolated rabbit ventricular myocytes (Shattock and Matsuura, 1993). Using this procedure, 5 min exposure to illuminated rose bengal reduced 7Na/K to 60% of control at 0 mV and to 75% of control at -75 mV. In the absence of extracellular potassium, no active ionic currents remain... 

The effect of cellular GSH depletion on /wa/K has also been studied using this model. Guinea-pig ventricular myocytes prepared from DEM-treated animals have been used to determine the effect of glutathione depletion on /xa/K- Myocytes prepared from DEM-treated animals showed a similar profile of glutathione content modification to that previously described in experiments using sarcolemmal homogenates. GSH levels in DEM-treated were reduced from a control value of 0.2 0.04 to 0.02 0.01 nmol/1 X10 cells. Jni/k at 0 mV was reduced from a control value of 1.1 0.12 to... 

Burton, K.P., Morris, A.C., Massey, K.D., Buja, L.M. and Hagler, H.K. (1990). Free radicals alterionic calcium levels and membrane phospholipids in cultured rat ventricular myocytes. J. Mol. Cell. Cardiol. 22, 1035-1047 (abstract). 

Fedida, D., Noble, D., Rankin, A.C. and Spindler, A.J. (1987). The arrhythmogenic transient inward current iTI and related contraction in isolated guinea-pig ventricular myocytes. J. Physiol. 392, 523-542. 

Goldhaber, J.I. and Weiss, J.N. (1993). Hydrogen peroxide increases sodium-calcium exchange in patch-clamped guinea pig ventricular myocytes loaded with Fura-2. Circulation, 88(4), 724, abstract. 

Shattock M. J. and Matsuura, H. (1993). Measurement of Na -K pump current in isolated rabbit ventricular myocytes using the whole-cell voltage-clamp technique. Inhibition of the pump by oxidant stress. Circ. Res. 72, 91-101. 

Williford, D.J., Sharma, V.K., Korth, M. and Sheu, S, S. (1990). Spatial heterogeneity of intracellular Ca concentration in nonbeating guinea pig ventricular myocytes. Circ. Res. 66, 234-241. 

Ventricular depolarization Change in the membrane potential of a ventricular myocyte, resulting in loss of polarization. Under... 

Quercetin and rutin suppressed photosensitized hemolysis of human erythrocytes with ho values equal to 40 p.mol l-1 and 150 jjlmt>I I 1, respectively [139]. Suppression of photohemolysis was accompanied by inhibition of lipid peroxidation. Morin inhibited oxygen radical-mediated damage induced by superoxide or peroxyl radicals to the human cells in the cardiovascular system, erythrocytes, ventricular myocytes, and saphenous vein endothelial cells [140]. Rutin protected against hemoglobin oxidation inside erythrocytes stimulated by prooxidant primaquine [141],... 

He J, Kargacin ME, Kargacin GJ, Ward CA (2003) Tamoxifen inhibits Na+ and K+ currents in rat ventricular myocytes. Am J Physiol 285(2) H661-H668... 

Liu XK, Katchman A, Ebert SN, Woosley RL (1998) The antiestrogen tamoxifen blocks the delayed rectifier potassium current, IKr, in rabbit ventricular myocytes. J Pharmacol Exp Ther 287 877-883... 

FIG. 3. Tight coupling in cardiac but not smooth muscle myocytes. Cells dialysed with 17 nM mobile Ca2+ buffer (EGTA). When depolarized, brief Ca2+ release events are seen in ventricular myocytes, indicating RyR gating occurs before the mobile buffer can scavenge the gating Ca2+ ions. Conversely, in smooth muscle cells CICR is completely blocked. The simplest interpretation of these data is that Ca2+ ions must traverse a distance of at least lOOnm, the distance beyond which the mobile buffer can prevent a rise in Ca2+. (From Collier et al 2000.)... 

Cheng H, Lederer WJ, Cannell MB 1993 Calcium sparks elementary events underlying excitation—contraction coupling in heart muscle. Science 262 740—744 Collier ML, Thomas AP, Berlin JR 1999 Relationship between L-type Ca2+ current and unitary sarcoplasmic reticulum Ca2+ release events in rat ventricular myocytes. J Physiol (Lond)... 

Isenberg, G. and Tamargo, J. (1985) Effect of imipramine on calcium and potassium currents in isolated bovine ventricular myocytes. European Journal of Pharmacology, 108, 121—131. 

Delpon, E., Tamargo, J. and Sanchez-Chapula, J. (1991) Further characterization of the effects of imipramine on plateau membrane currents in guinea-pig ventricular myocytes, hiaunyn-Schmiedeberg s Archives of Pharmacology, 344, 645-652. 

Mitcheson, J.S. and Hancox, J.C. (1999) An investigation of the role played by the E-4031 sensitive (rapid delayed rectifier) potassium current in isolated rabbit atrioventricular nodal and ventricular myocytes. Pflugers Archiv European Journal of Physiology, 438, 843-850. 

In vitro Disaggregated cells Repolarizing currents (e.g., IKs, IK1, Ito), depolarizing currents (e.g., INa) currents, ICa (whole cell patch-clamp) Disaggregated cells ventricular myocytes mouse atrial tumor cells (AT-1) immortalized cardiac muscle cells (HL-1) Jost et al.,-65 Liu and Antzelevitch 66 Jurkiewicz and Sanguinetti 67 Li et al. 68 Yang and Roden 69 Banyasz et al. 70 Xia et al.71... 

Banyasz, T., Fulop, L., Magyar, J., Szentandrassy, N., Varro, A., and Nanasi, P.P, Endocardial versus epicardial differences in L-type calcium current in canine ventricular myocytes studied by action potential voltage clamp, Cardiovasc. Res., 58, 66-75, 2003. 

Suetake, I., Takisawa, H., and Nakamura, T., Related contractile activity and fluorescence changes in fluo-3-loaded isolated ventricular myocytes, Jpn. J. Physiol, 42, 815-821, 1992. 

A benzopyran derivative, RP-58866 (70) is under development by Rhone-Poulenc. Patch clamp studies in guinea-pig ventricular myocytes indicate that RP-58866 inhibits the inward rectifying potassium current (7ki) with no effects on the delayed rectifier, ATP-sensitive potassium currents or calcium currents [200]. RP-58866 increases APD90 of Purkinje fibres by about 45% at 0.3 yuM without affecting K ax [201]. The compound was effective... 

At 0.1 and 0.3 /iM the compound significantly prolonged APD of guinea-pig papillary muscle with little effect on F ax [208]. At a much higher concentration (100 //M), Umax was significantly inhibited. Voltage-clamp studies with single ventricular myocytes showed that TYB-3823 blocked outward potassium currents. Further studies in vascular tissue indicated that it also blocks a- and / -receptors [209]. This may also contribute to its antiarrhythmic profile. 

In normal atrial and ventricular myocytes, phase 4 is electrically stable, with the resting membrane potential held at approximately -90 mV and maintained by the outward potassium leak current and ion exchangers previously described. It is during phase 4 that the Na+ channels necessary for atrial and ventricular myocyte depolarization recover completely from inactivation. In myocytes capable of automaticity, the membrane potential slowly depolarizes during this period to initiate an action potential (discussed later). 

Dofetihde increases the ERP of ventricular myocytes and Purkinje fibers. The ERP-prolonging effect on the ventricular tissue is somewhat less than that in atrial tissue. 

Dofetilide does not significantly alter the mean arterial blood pressure, cardiac output, cardiac index, stroke volume index, or systemic vascular resistance. There is a slight increase in the delta pressure/delta time (dP/dt) of ventricular myocytes. 

The effects on the A-V node may result in a conduction block and the termination of tachycardias that use the A-V node as a Umb of a reentrant circuit. Adenosine does not affect the action potential of ventricular myocytes because the adenosine-stimulated potassium channel is absent in ventricular myocardium. 

In general, in various parts of the conduction system higher amounts of connexin were found especially in the fast conducting tissues as compared to ventricular myocardium. Only minimal expression of Cx37 and Cx46 between occasional atrial and ventricular myocytes has been observed [Davis et al.,... 

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