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How does β‐adrenergic stimulation increase the heart rate? The role of intracellular Ca 2+ release in amphibian pacemaker cells
Author(s) -
Ju YueKun,
Allen David G.
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.0793u.x
Subject(s) - stimulation , amphibian , intracellular , adrenergic , medicine , chemistry , biophysics , endocrinology , cardiology , biology , receptor , biochemistry , ecology
1 The mechanism by which sympathetic transmitters increase the firing rate of pacemaker cells was explored in isolated cells from the sinus venosus of the cane toad Bufo marinus . Intracellular calcium concentration ([Ca 2+ ] i ) was measured with indo‐1 and membrane potential and currents were recorded with the nystatin perforated‐patch technique. 2 Adrenaline or isoprenaline (2 μM) increased the transient rise in [Ca 2+ ] i and increased the firing rate; these effects were blocked by propranolol (2 μM). 3 To determine whether the changes in [Ca 2+ ] i might influence the firing rate we studied agents which affect either the loading or the release of Ca 2+ from the sarcoplasmic reticulum (SR). Rapid application of caffeine (10 mM) to spontaneously firing cells caused a large Ca 2+ release from the SR and the cells were then quiescent for 24 s. In the presence of β‐adrenergic stimulation the caffeine‐induced [Ca 2+ ] i was 14 % larger but the period of quiescence after application was reduced to 12 s. 4 Ryanodine, at either low (1 μM) or high (> 10 μM) concentration, stopped firing. However, when the SR store content of Ca 2+ was tested with caffeine, at low ryanodine concentration the SR Ca 2+ store was empty whereas at the high concentration the SR store was still loaded with Ca 2+ . β‐Adrenergic stimulation was not able to restore firing at the low concentration of ryanodine but did restore firing at the high ryanodine concentration. 5 An SR Ca 2+ pump blocker, 2,5‐di(tert‐butyl)‐1,4‐hydroquinone (TBQ) which depletes the SR store of Ca 2+ , also rapidly and reversibly stopped spontaneous firing. 6 The relation between the amplitude of the [Ca 2+ ] i transient and firing rate established in the presence of ryanodine was similar when firing was restored by β‐stimulation. 7 In both spontaneously firing and voltage‐clamped cells, depleting the SR store with either ryanodine or TBQ suggested that about half of the Ca 2+ which contributes to the calcium transient is released from the SR. 8 These results show that the amplitude of the [Ca 2+ ] i transient is an important factor in the firing rate of toad pacemaker cells and consequently agents which modify SR Ca 2+ release influence firing rate. The effects of β‐stimulation on firing rate seem to be largely mediated by changes in amplitude of the [Ca 2+ ] i transient.