Cellular Electrophysiological Changes Research Articles

EFFECTS OF ACUTE HYPOXIA ON CELLULAR ELECTRICAL PROPERTIES OF THE SINUS NODE (SN) AND ATRIUM

The heart rate and arrhythmogenic effects of acute hypoxia (H) are incompletely understood. Some studies have suggested a differential effect of H dependent upon the extent to which Ca and Na participate in the action potential (AP). We studied the effects of acute, severe H on SN and atrial parameters using rabbit preparations and standard microelectrode techniques. AP from true SN pacemaker cells (dependent on the slow inward Ca current (isi)) were most effected by H. There were significant (p·0.05) decreases in spontaneous rate, AP amplitude (APA), maximum dia stolic potential (MDP) and slope of phase 4 depolarization. Corrected SNRT and SACT were markedly increased. H produced SN entrance block, pacemaker shifts and ectopic activity in many preparations. AP from subsidiary SN cells (a two component AP dependent on Na and Ca) were less effected by H. There were only moderate decreases in APA and MDP. AP from atrial muscle are very dependent on the fast Na current for depolarization. H produced no changes in APA, MDP or Vmax. AP duration (at 50 and 90% repolarization) and atrial effective refractory period were significantly shortened by H. The decrease in AP duration (due to shortening of the plateau) may be related to H induced decreases in the Ca isi. In summary, many of the arrhythmias resulting from clinical H can be explained by the observed changes in cellular electrophysiology. There appears to be a high sensitivity of Ca dependent channels (and AP) to the effects of H.

Fetal canine cardiac Purkinje fibers: electrophysiology and ultrastructure.

We studied the ontogenesis of the transmembrane action potential and the ultrastructure of fetal canine Purkinje fibers. Fetal hearts were obtained from fetuses just after implantation to end gestation. Using standard microelectrode recording techniques, we found that action potential characteristics varied linearly over this period of development. Maximum diastolic potential (MDP) ranged from -65 to -85 mV; action potential amplitude (AMP) varied from 100 to 120 mV; maximum upstroke velocity (Vmax) increased from 200 to 550 V/s. Action potential duration measured to 50% repolarization (APD50) increased from 15 to 156 ms while duration measured at full repolarization (APD100) similarly increased from 75 to 236 ms. The relationship between external potassium concentration and membrane potential was equivalent across all stages of fetal development. Tetrodotoxin (TTX, 7.7 X 10(-7) to 1.6 X 10(-5) M) caused concentration-dependent decreases in AMP, Vmax, and APD50. Verapamil (1 X 10(-7) to 1 X 10(-5) M) decreased Vmax and APD50 in a concentration-dependent manner. The effects of both TTX and verapamil were statistically equivalent across all stages of fetal development. Ultrastructural studies of fetal Purkinje fibers showed that myocytes at the earliest stages of development (Purkinje fibers were not visually distinct at this time) were arranged as a tightly packed mosaic with a rounded shape, with a large amount of glycogen, small sparse mitochondria, and relatively large nuclei. Mitotic cells were observed frequently. Purkinje fibers when first identified grossly had fewer myofilaments than working myocardial cells and sarcomeres without M lines. By late gestation, intercalated disks appeared with an increase in surface areas; desmosomes occurred more frequently. Myofilaments are organized around Z bands into rudimentary sarcomeres that still lack M lines. These data indicate that, although the fetal canine Purkinje fiber undergoes marked developmental changes in ultrastructure, cellular electrophysiological changes are more subtle. The action potential has a qualitative appearance similar to those of the neonatal or adult fiber. At no time during fetal development could we find slow-response action potentials.

Arrhythmias and cellular electrophysiological changes during myocardial "ischaemia" and reperfusion.

Action potentials and ECGs were recorded from isolated guinea pig hearts during low flow (10% of control) and zero flow myocardial "ischaemia" and during subsequent reperfusion. During myocardial "ischaemia" ventricular tachycardia and ventricular fibrillation were significantly more frequent during low flow, than zero flow "ischaemia" (P less than 0.01). Reperfusion arrhythmias required a minimum ischaemic period of 10 to 15 min, were most frequent following 20 to 30 min of "ischaemia", being fewer following 60 min of "ischaemia" (P less than 0.05). The degree of "ischaemia" had little effect on reperfusion arrhythmias following 20 to 30 min of "ischaemia". Both types of "ischaemia" reduced action potential amplitude, Vmax, and duration, and increased conduction time. During low flow "ischaemia", electrophysiological change reached a nadir at 12 +/- 3 (mean +/- SEM) min, and in all cases spontaneous electrophysiological recovery in action potentials and conduction time preceded ventricular arrhythmias, which occurred at 18 +/- 3 min. In contrast during zero flow "ischaemia" electrophysiological changes were more marked and no recovery was observed. Refractory periods were initially prolonged by both forms of "ischaemia", followed by a marked shortening. The initial prolongation was more marked and subsequent shortening less during zero than low flow "ischaemia". Reperfusion induced electrophysiological recovery in all hearts; however reperfusion VF was preceded by further shortening of action potential duration and refractory period. These results indicate that residual flow during myocardial "ischaemia" is associated with spontaneous electrophysiological recovery and more frequent ventricular arrhythmias. The severity of "ischaemia" is less important than its duration for the development of reperfusion arrhythmias.

Cellular electrophysiological changes in "round heart disease" of turkeys: a potential basis for dysrhythmias in myopathic ventricles.

Arrhythmias are commonly recorded in "round heart disease", a presumed viral, congestive cardiomyopathy of turkeys. To assess whether cellular electrophysiological changes may be associated with arrhythmia susceptibility, we compared transmembrane action potential characteristics in left and right ventricular endocardial muscle fibres from 19 inbred myopathic turkeys with findings in 13 normal control turkeys (age 1 to 74 days). In left ventricular tissue, as a group, action potential duration at 50% repolarisation (APD50) was reduced in myopathic hearts (201+/-6(SEM) vs 228+/-9 ms in controls. P less than 0.01), while the maximum rate of phase 0 (dV/dtmax) action potential amplitude, diastolic resting membrane potential and action potential duration at 90% repolarisation (APD90) did not differ from control turkeys. By contrast, in myopathic right ventricular tissue, as a group, both APD50 (186+/-5 vs 206+/-4 ms in controls) and APD90 (208+/-4 vs 228+/-3 ms in controls) were shorter (P less than 0.01). The plateau potential in both right and left ventricular tissue was significantly higher in inbred turkeys. Since a spectrum of cardiac dilatation and hypertrophy is present in myopathic turkeys, we examined the effect of hypertrophy on action potential characteristics. In "round heart disease" turkeys, left ventricular hypertrophy was characterised by reduced dV/dtmax (98+/- vs 274+/-26 V.s-1, P less than 0.01) and right ventricular hypertrophy by further shortening of both APD50 (174+/-7 vs 202+/-6 ms, P less than 0.01) and APD90 (193+/- vs 224+/-5 ms, P less than 0.01), but no change in dV/dtmax (105+/-13 vs 120+/-9 V.s-1, P = NS). These results indicate that certain electrophysiological differences (eg reduced action potential duration), may, in part, contribute to dysrhythmia susceptibility in this presumed viral cardiomyopathy model.

Effects of axotomy on lamprey spinal neurons

The central axonal processes of dorsal cells of larval sea lampreys were cut by a high spinal transection. Subsequent histologic changes included a loss of cytoplasmic basophilia, nuclear eccentricity, the development of a perinuclear basophilic shell, and a slight decrease in cell diameter and increase in nuclear diameter resulting in a 26% increase in the ratio of nucleus to cell diameter. These changes were maximal at 3 weeks and were related to the proximity of the cell to the transection site. Electrophysiologic changes included increased input resistance, increased voltage and current thresholds for spike initiation, decreased maximal rate of rise of action potentials, increased spike width, and increased spike overshoot. There was also an increase in axonal conduction velocity and a reduction in resting membrane potential. The electrophysiologic changes tended to lag behind the histologic changes by 1 to 2 weeks and were not clearly related to the proximity of the cell to the transection site. The cellular electrophysiologic changes could result from a decrease in the densities of sodium and potassium channels of the membrane, but there is no evidence yet to support this or any other specific hypothesis.