2 The free internal Ca+ concentration in human red cells is set according to the leak­ 2 and-pump principle: There is a finite passive Ca+ influx at the physiological 2 2 Ca+ -gradient across the membrane which is compensated by Ca+ pumping in the outward direction with a rate given by the degree of saturation of the A TP-fuelled Ca­ 2 pump at the steady-state internal Ca+ concentration. Simons (1982) recently devised a method allowing the measurement of the steady­ 2 2 state internal Ca+ concentration. Cells are suspended in media of different Ca+ con­ 2 2 tent whose Ca+ concentration is monitored by a Ca+ -selective electrode. When the cells are lysed (by digitonin) there is an upward or downward deflection of the elec­ 2 trode signal. At the point of zero deflection, the cellular Ca+ concentration equals that 2 of the medium. The result is, that in fresh human red blood cells the Ca+ concentra­ tion is ;;;; O.4,uM (this is an upper estimate; the true value may be considerably lower).

I: Introductory considerations.- The major steps in the discovery of calcium entry blockers..- Basic mechanisms and classification of calcium entry blockers..- Calcium entry blockers: perspectives..- Twenty-seven calcium entry blockers in development: a new chapter in pharmacology..- II: Calcium entry blockers and peripheral circulatory function..- Calcium-ions and excitation contraction coupling in vascular smooth muscle cells..- Laser microprobe mass analysis (LAMMA) as a technique to quantitate Ca2+ ions..- Vascular pharmacology of calcium entry blockers..- Calcium homeostasis in human red blood cells..- Impact of Ca2+ entry blockers on Ca2+ dependent mechanisms in red blood cells, platelets and endothelial cells..- Red blood cell microrheology and calcium antagonists..- Calcium e ntry blockers in the treatment of peripheral obliterative arterial disease..- III: Calcium entry blockers and myocardial function..- Pharmacology of calcium entry blockers in animal and human coronary arteries..- Calcium paradox and calcium entry blockers..- Myocardial oxygen deprivation and calcium deprivation: ultrastructural characteristics and clinical significance..- Basic and clinical aspects of myocardial protection by calcium entry blockers..- Effect of calcium entry blockers on impaired left ventricular wall motion..- The influence of Ca2+ entry blockers on hemodynamics and coronary blood flow, and its importance for the treatment of angina pectoris..- The use of selective calcium antagonism in variant (vasospastic) and classical (effort) angina pectoris..- Calcium entry blockers in cardiovascular therapy. Influence of diltiazem on hemodynamics and coronary blood flow..- IV: Calcium entry blockers and cerebral function..- Calcium entry blockers and cerebral function: an introduction..- Calcium entry blockers and cerebral resuscitation..- Effect of calcium entry blockers in models of brain hypoxia..- Calcium entry blockers in the therapy of vertebrobasilar insufficiency..- Calcium entry blockers and pharmacological aspects of migraine..- Clinical evaluation of calcium entry blockers in migraine..- V: Calcium entry blockers in hypertension treatment..- Double-blind comparison of the antihypertensive effects of verapamil and nifedipine..- Treatment of hypertension emergencies and chronic arterial hypertension with calcium entry blockers..- The effect of nifedipine on arterial pressure and reflex cardiac control..- Concluding remarks.- Why are Ca2+ entry blockers effective in the treatment of hypertension and tissue hypoxia?.- List of authors and co-authors.