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Effects of caffeine on intracellular sodium activity in cardiac Purkinje fibres: relation to force
Author(s) -
Iacono Giovanni,
Vassalle Mario
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb16207.x
Subject(s) - caffeine , chemistry , endocrinology , inotrope , medicine , tetrodotoxin , calcium , sodium , organic chemistry
1 An increase in cytoplasmic calcium by caffeine would lead to Ca extrusion via the Na/Ca exchange. The hypotheses were investigated that, as a consequence, caffeine might increase intracellular sodium activity (a i Na ) and that the relation between a i Na and force might be conditioned by the Ca load. 2 Action potential, a i Na and contractile force were recorded in sheep Purkinje fibres during exposure to caffeine under conditions that decrease or increase the Ca load by different mechanisms. 3 In Tyrode solution, caffeine (8 m m ) increased a i Na from 8.05 ± 0.20 to 10.52 ± 0.40 m m (+ 30.5%) and had a triphasic effect on force: an initial transient increase (+ 93.6%), a subsequent decrease (‐37.1%) (negative inotropy) and slow partial recovery (+8.9%). 4 Decreasing the Ca load by means of manganese (1 m m ) decreased a i Na and force. Adding caffeine re‐increased a i Na and no longer caused a negative inotropic action. Cadmium (0.2 m m ) also decreased a i Na , and caffeine reincreased it although far less than in Tyrode solution. 5 High [K] o (10 m m ) and tetrodotoxin (5 μ m ) decreased a i Na as well as force. In their presence, caffeine re‐increased a i Na and no longer had a negative inotropic action. 6 Increasing the Ca load by means of high [Ca] o (8.1 m m ) increased force (+ 195%) and decreased a i Na , (‐20.3%). Adding caffeine re‐increased a i Na (+ 28.1%), but immediately decreased force (‐32.3%). 7 Addition of pyruvate (10 m m ) to caffeine increased force, as it does in the presence of Ca overload. 8 Noradrenaline (0.1–1 μ m ) decreased a i Na and increased contractile force. In its presence, caffeine de creased a i Na further and in creased force. 9 It is concluded that caffeine increases a i Na , even during the negative inotropic effect. The decrease in force appears to depend on Ca load. Thus, caffeine no longer decreases force under conditions that decrease Ca load (Mn, high [K] o , TTX) and immediately decreases force when the Ca load is increased (high [Ca] o ). However, in the presence of noradrenaline, caffeine de creases a i Na and markedly in creases force, as the Ca load is increased, but Ca can be removed from the cytoplasm into the SR.