Mechanisms of Suppression and Initiation of Pacemaker Activity in Guinea-pig Sino-Atrial Node Superfused in High [K+]o

• Published in: Journal of molecular and cellular cardiology 1997-05, Vol.29 (5), p.1433-1445
• Main Authors: Kim, E.M., Choy, Y., Vassalle, M.
• Format: Article
• Language: English
• Subjects: Animals; Barium; Barium - pharmacology; Calcium; Calcium - pharmacology; Cesium; Cesium - pharmacology; Dose-Response Relationship, Drug; Electrophysiology; Female; Guinea Pigs; High [K+]o; In Vitro Techniques; Male; Nickel; Nickel - pharmacology; Nifedipine; Nifedipine - pharmacology; Oscillatory afterpotentials and prepotentials; Pacemaker potential; Potassium - pharmacology; Sinoatrial Node - drug effects; Sinoatrial Node - physiology; Sino–atrial node automaticity; Sodium - pharmacology; Tetrodotoxin
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1006/jmcc.1997.0382

The electrophysiological mechanisms by which changes in [K+]osuppress and initiate pacemaker activity were studied in guinea-pig isolated sino–atrial node (SAN) superfusedin vitro. High [K+]o(10 mmor higher) gradually decreases maximum diastolic potential and action potential amplitude, until only subthreshold responses and eventually quiescence follow. When the threshold potential is missed, an oscillatory afterpotential (Vos) is often superimposed on early diastolic depolarization (DD). During the subsequent late DD, gradually increasing oscillatory prepotentials (ThVos) appear, whose depolarizing phase may initiate an action potential. If ThVosmiss the threshold, they gradually decrease in size. In quiescent SAN, on decreasing high [K+]o, the resumption of spontaneous activity is caused by ThVos. In high [K+]o, Cs+and Ba2+may induce spontaneous activity in quiescent SAN and accelerate spontaneously active SAN. A low [Ni2+]odoes not suppress SAN, whereas nifedipine blocks excitation (but not DD); and high [Ca2+]oinduces spontaneous discharge in quiescent SAN. Tetrodotoxin and low [Na+]ooften cause block of conduction. In conclusion, high [K+]osuppresses SAN discharge not by abolishing DD, but by preventing the attainment of the threshold. A slower rhythm may be maintained by ThVosarising during the late DD. After arrest, resumption of activity is due to gradually increasing ThVos. The effects of current blockers suggest that in high [K+]othe mechanism underlying DD may involve IK, but not Ifor ICa. Initiation of discharge by high [Ca2+]oand induction of quiescence by nifedipine suggest a role of Ca2+in excitation (but not in DD). The effects of tetrodotoxin and low [Na+]osuggest a role of Na+in conduction within SAN superfused in high [K+]o.