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Effects of caffeine on aritlmetic skill test and hemodynamic effects were investigated after drinking caffeine-free or caffeine-containing (180mg) coffee. The development of tolerance in habitual coffee-drinkers was also examined. A double-blind study of 417 healthy medical university students (22.4±2.1 years old) was carried out. Ten rounds of the arithmetic tests were performed; the first four rounds before, and the subsequent six rounds after a coffee-break. Each round was composed of three 1-min arithmetic tests and two 1-min rests between the tests. The arittmetic skill per round was averaged. Simultaneously, heart rate and blood pressure were also measured once a round. The mean value of arithmetic skill at the 4th round before coffee-break was 86.7±3.9/ min (n=417). The heart rate and mean blood pressure were 73.7±3.3 beats/min and 85.7 ±3.8 mmHg. As compared with caffeine-free group (n=205), caffeine-containing groups had a significant enhancement of arithmetic skill at 45 to 60 min later. The mean blood pressure increased at 15 to 90 min, but the heart rate was unaffected. Simultaneously, the serum concentration of caffeine increased from 0.9±0.3 to 4.3±1.6 ptg/ml (n=12, P

Electrophysiological and mechanical effects and alteration of intracellular Ca²⁺ concentration in canine ventricular muscle by amiloride, a potassium sparing diuretic drug, were examined, using conventional microelectrode technique and fura-2 Ca²⁺-sensitive fluorescent dye. Amiloride (50 μM) depressed the action potential amplitude by 8.2±1.4% (n=8, P

Effects of ATP-dependent K⁺ channel openers on the action potentials and the contractile force in canine cardiac Purkinje fibers were examined. Cromakalim and pinacidil (0.3 to 10 μM), and nicorandil (0.3 to 1 mM) shortened both the 50% and 90% action potential durations (APD), and decreased the contractile force, in a concentration and frequency-dependent manner. These responses were reversible. The APD shortening and the negative inotropic effect induced by a switch of stimulation frequency (from 0.5 to 3 Hz) were potentiated by application of the openers. Other action potential parameters were unaffected, but the resting potential of relatively less negative voltage was hyperpolarized. These effects were potently antagonized by glibenclamide (a selective blocker of ATP-sensitive K⁺ channel). Under the calcium overload condition, the K⁺ channel openers abolished a delayed afterdepolarization and recovered the contractile force. These results suggest that the ATP-sensitive K⁺ channel openers increase the K⁺ conductance and simultaneously may possess cardioprotective actions to reduce the cellular Ca²⁺ level in calcium overloaded cells.

Whole-cell patch clamp experiments were performed to examine the underlying currents to generate spontaneous activity in freshly isolated single longitudinal muscle cells of pregnant rat uterus (18-day gestation). Isolated single cells were spindle- or round-shaped (50-700 μm in length and 2-30 μm in diameter). The holding potential was -30 mV. Long-duration (3 sec) hyperpolarizing pulses were applied to -40 to -120 mV, in increments of 10 mV. Experiments were performed at room temperature (22℃). A hyperpolarization-activated inward current (I_f) was produced. Current density at -120 mV was -1.03±0.31 pA/pF (n=5). The average capacitance was 64.3±2.3 pF (n=8). The threshold potential for activation of I_f was about -50 to -60 mV. The reversal potential was -18.6±2.1 mV (n=4). In the presence of Cs⁺ (3 mM), the I_f current at -120 mV was decreased by 76.5±2.1% (P

Electrophysiological effects of flecainide and ethacizin (class Ic antiarrhythmic drugs) were examined using conventional microelectrode techniques. Flecainide significantly depressed the maximum rate of depolarization (⩒max) at 3x10⁻⁶M, and depolarized the resting potential (RP) at 10⁻⁵M, in a concentration-dependent manner. Ethacizin depressed ⩒max at 10⁻⁶M, and depolarized RP at 10⁻⁵M, significantly. However, both drugs did not affect the effective refractory period (ERP) nor the action potential duration (75% repolarization, APD₇₅). Both also had no effect on the action potential amplitude (APA). On the other hand, the drugs caused a use (or rate)-dependent block of ⩒max, and their time constants of onset of inhibition (at 3 Hz) were slow ; 6.3±1.2 msec (n=10) in the presence of flecainide (10⁻⁵M), and 6.0±1.6 msec (n=6) in the presence of ethacizin (10⁻⁵M). The time constants of the recovery were also so late : 12.2±2.5 sec (n=3) for flecainide (10⁻⁵M), and 27.1±13.3 sec (n=3) for ethacizin (2x10⁻⁶M), These results indicate that both antiarrhythmic drugs, flecainide and ethacizin, have no effect on APD₇₅ and ERP, but possess the characteristics for very slow kinetics of the use-dependent block and the recovery for fast Na⁺ channels of cardiac muscles. Ethacizin produces slower kinetics for the Na⁺ channels than flecainide.

Effects of caffeine on arithmetic performance were investigated with 99 university students. A double-blind study for arithmetic skill test was carried out, after drinking caffeine-free or caffeine-containing (180 mg) coffee. Eight rounds for the arithmetic tests were performed ; four rounds before, and four rounds after coffee break. Each round was 1-min arithmetic tests three times with 1-min intervals. The arithmetic skill and the ratio of arithmetic errors per each round were averaged. Simultaneously, heart rate was also measured. The mean values of arithmetic skill and the ratio of errors at the 4th round (n=99) were 81.4±1.7/min and 0.28±0.02%. The heart rate was 76.9±1.5 beats/min. Before and after coffee-drinking, arithmetic skill was enhanced, whereas the heart rate was significantly decreased. As compared with the caffeine-free group, caffeine significantly enhanced the arithmetic skill 45 and 60 min after coffee-drinking. But the ratio of arithmetic errors was not affected. The heart rate was significantly decreased only at 45 min later. These results indicate that caffeine (-containing coffee drinking) can enhance arithmetic skill and decrease the heart rate, presumably resulting from stimulation of the central nervous system.