The SA nodal pacemaker activity is regulated dominantly by autonomic nervous elements, i.e., sympathetic and parasympathetic nervous factors. In addition, circulatory bioactive substances and physicochemical factors also modify changes in sinus rate. Exogenously applied substances exert their actions on sinus rate directly and/or indirectly. The mechanisms of bradycardia and tachycardia induced by electrical nerve stimulation or exogenous substances are reviewed mostly by describing the results from experiments in isolated canine SA node preparations which were perfused with blood. In this review, newly developed bradycardic agents are introduced in addition to descriptions of numerous active substances developed in the past.
Ion-selective electrodes have been used for many years to analyze ion activities in electrolyte solutions. In recent years, these electrodes have been miniaturized and applied for measurements in the cell interior. This article describes basic principles for both the fabrication and the intracellular application of ion-selective microelectrodes, particularly focusing on double barreled liquid ion-exchanger microelectrodes. The use of ion-selective microelectrodes allows continuous and real-time measurements of intracellular ion activities of a single cell in both multicellular and isolated cell preparations under various conditions, such as changes in ion composition of the extracellular bathing fluid and exposure to certain drugs. With double-barreled ion-selective microelectrodes, the transmembrane potential and intracellular ion activities can be measured simultaneously in the same cell. Although there are still some problems or limitations to the intracellular application of ion-selective electrodes, this technique is useful for determining the actual movement of intracellular ions, and thereby to elucidate cellular mechanisms of membrane transport and other physiological functions.
We used a Fotonic Sensor™, a fiber optic displacement measurement instrument, to measure the chronotropy and the contractility of cultured neonatal rat cardiac myocytes. The principle of the measurement is to detect changes in the distance between the probe and myocytes vertically extruded by the contraction. A fiber optic probe consists of adjacent pairs of light-transmitting and light-receiving fibers. The ratio of reflected light to transmitted light changes proportionally to the distance between the probe and an object at a certain range shown in a calibration curve. The analogue output from the sensor was transferred to a personal computer through an analogue/digital converter and analyzed. The sensor was able to detect the rate of myocyte beating, i.e., chronotropy, with a high correlation to the frequency of electrically stimulated beating and agreed well with the beating rate counted visually under a microscope. The contractility was evaluated by the maximum contraction velocity (Vm) by the first derivatives of the contraction curves obtained by the sensor. Norepinephrine (NE) and isoproterenol (ISO) increased the contractility in cultured myocytes in a dose-dependent fashion. In the preparation of rat ventricular papillary muscle, NE- and ISO-induced increase in the Vm in the radial direction significantly correlated with the increase in tension measured with a force-displacement transducer. These results indicate that the Fotonic Sensor™ is an appropriate instrument for evaluating the chronotropy and the contractility of cultured myocytes.