A pace‐maker‐like current in the sheep atrium and its modulation by catecholamines.

Abstract

SUMMARY1. A modified single-sucrose-gap system was used to study sheep atrial trabeculae under voltage-clamp conditions. 2. A time-and voltage-dependent current system is described, which resembles the current if in Purkinje fibres. This current was activated at membrane potentials of between -60 and -70 mV in many fibres. The addition of Ba2+ reduced the instantaneous current (the 'jump') and thus facilitated the study of the current if.Current tails were more prominent in the presence of TTX and Mn2+. Most experiments were done in the presence of Ba2+, M2+ and TTX. 3. Standard envelope tests and conductance measurements indicated that this current is an inward current, activated on hyperpolarization. We have also labelled the atrial current if.4. The instantaneous fully activated current-voltage relationship, i(E) was found to be linear in the activation range. Increasing the level of K+ , which increased the current magnitude, also increased the slope of the i(E) curve. The current magnitude was also dependent on the level of Na+ in the medium.5. The current magnitude was increased by adrenaline or isoprenaline. Only a small part of the increase could be attributed to a shift in the voltage dependence of the gating kinetics. The shifts in activation curves were much smaller (3-4 mV in the depolarizing direction) than those in Purkinje fibres.6. Large shifts in activation curves were obtained with theophylline, indicating that the presence of Ba2+ or Mn2+ did not occlude any shifts by adrenaline. The magnitude of if was increased by theophylline, with a further increase by adrenaline. There is therefore no mutual occlusion of the two effects on if.7. The slope of the i(E) curve was increased by isoprenaline, indicating that there was an increase in conductance. The presence of propranolol did not prevent the increase in current amplitude by isoprenaline. A direct effect of catecholamines on the channel is suggested.

Effects of potassium conductance inhibitors on spontaneous diastolic depolarization and abnormal automaticity in human atrial fibers

“…However, 4-AP effects on DD could as well be explained by a decrease in iK1 (20) leading to an increase in the depolarizing effect of if as observed with barium or low K + solutions. Modifications of diastolic depolarization, similar to those observed with 4-AP, were also produced by epinephrine or dopamine, both known to increase if (4,8).…”

“…In animal models (9,18), the application of a constant depolarizing current to myocardial preparations is sufficient to induce autorhythmicity (depolarization-induced automaticity), possibly because this: (i) drives the membrane potential to a range favorable to K and Ca pacemaker current intervention; (ii) partially counterbalances the hyperpolarizing effects of background K current. Indeed, pacemaker currents have been shown to be present also in non-specialized myocardial cells, particularly in the atrium (1,4,16). In the normal state, these currents do not lead to diastolic depolarization because a large background K conductance offers strong resistance to their depolarizing effects and main-tains the membrane potential near the equilibrium potential for K ions, as in ventricular muscle (13).…”

Ionic currents activated during hyperpolarization of single right atrial myocytes from cat heart.

“…Atrial myocytes were isolated by methods modified from Silver et al, 8 Lee,9 and Bechem et al 10 After a midsternal thoracotomy, the heart was quickly removed and mounted on a Langendorff perfusion apparatus. The heart was perfused for 5 minutes with a Tyrode's solution containing (mM) NaCl 137, KCl 5.4, CaCl2 1.8, MgCl2 1.0, NaHCO3 12, NaH2PO4 0.6, and glucose 11 and saturated with 95% 02-5% CO2 to yield a pH of 7.4. This procedure was followed by a 5-minute perfusion with a nominally Ca2+-free Tyrode's solution and a final perfusion for 50-60 minutes with a Tyrode's solution containing 36 ,uM Ca2 , 0.1% albumin, and 0.06% collagenase (type II, Worthington Biochemical Corp., Freehold, N.J.; 163 units/mg).…”

Pacemaker current in single cells and in aggregates of cells dissociated from the embryonic chick heart.

“…6, which contains results from a 200 ,am diameter aggregate of 7-R. M. BROCIU, J. R. CLAY AND A. SHRIER day-old atrial cells and a two-cell cluster of 7-day-old atrial cells, Fig. 6A Step Earm, Shimoni & Spindler, (1983). The time-independent, net inward background current (the instantaneous current jumps in Fig.…”