쥐의 좌심방에서 세포막을 통한 Ca²⁺ Flux에 영향을 주는 약물이 자극빈도-장력 곡선에 미치는 영향

The Influence of Several Drugs Affecting Ca²⁺ Influx on Frequency-tension Curve of Rat Left Atrium

Cardiac muscles show stimulation frequency-dependent tension changes i.e. Bowditch phenomenon and Woodworth phenomenon, the former is an increase of tension with the increase of stimulation frequency, whereas the latter is an increase of tension with a decrease of stimulation frequency. Bowditch phenomenon is seen in the range of frequency 1.0 cps and above, and Woodworth phenomenon below the frequency 1.0 cps in the most of mammalian cardiac atrium. To throw some light on the possible mechanism of both phenomena in rat atrium, influences of drugs affecting Ca²⁺ influx through the plasma membrane (verapamil, La³⁺, norepinephrine) and Ca²⁺ release from sarcoplasmic reticulum (SR) on frequency-tension curve were studied. The results obtained are summarized as follows: 1) At low temperature (27.5℃), both Bowditch and Woodworth phenomenon were demonstrated. But Bowditch phenomenon disappeared at the temperature above (32.5℃). 2) At (27.5℃), in the presence of verapamil, a Ca²⁺ channel blocker, a time course of change in the frequency-tension was studied. It was found that Bowditch phenomenon was affected before the Woodworth phenomenon, then the former was completely disappeared. At (32.5℃), where no Bow-ditch is seen in normal atrial muscle, Bowditch phenomenon was reappeared by an administration of norepinephrine suggesting again that slow inward current of such as Ca²⁺ channel is closely related to Bowditch phenomenon. 3) At 27.5℃, in the presence of La³⁺, although tensions were decreased at all stimulation frequencies, Bowditch and Woodworth phenomenon were still demonstrated. However in the presence of both La³⁺ and verapamil, Bowditch phenomena was disappeared suggesting that La³⁺ is less effective in blocking Ca²⁺ channel than verapamil. 4) At 27.5℃, in the presence of ryanodine, an inhibitor of calcium release from SR, Woodworth phenomenon was disappeared, which was consistent with previous reports of others, suggesting that Ca²⁺ release from SR is closely related to Woodworth phenomenon. From the above findings, it may be concluded that Bowditch phenomenon is dependent on the magnitude of Ca²⁺ influx through slow channel and Woodworth phenomenon is dependent on the amount of Ca²⁺ stored in SR.