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Dissimilar Action of Two Cyclic Adenosine‐Monophosphate Analogues on the Sodium Current in Intact Rat Papillary Muscle
Author(s) -
KIRSTEIN MICHAEL,
LANGENFELD HEINER,
KATZER ASTRID,
KOCHSIEK KURT
Publication year - 1994
Publication title -
pacing and clinical electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.686
H-Index - 101
eISSN - 1540-8159
pISSN - 0147-8389
DOI - 10.1111/j.1540-8159.1994.tb03802.x
Subject(s) - medicine , adenosine , cyclic adenosine monophosphate , endocrinology , papillary muscle , intracellular , second messenger system , biophysics , sodium , resting potential , membrane potential , electrophysiology , receptor , biochemistry , chemistry , biology , organic chemistry
In intact papillary muscles from rat we have found with the loose‐patch‐clamp technique an increase of the fast cardiac sodium current (I Na + ) by isoproterenol (ISO). In this study we have tested two membrane permeable analogues of the intracellular second messenger cyclic adenosine‐monophosphate (cAMP) to investigate the intracellular pathway: 8‐Br‐cAMP (50 μM) and the newer developed S p 5,6‐Dichloro‐1‐β‐D‐ribofuranosylbenzimidazole‐3′, 5′‐cyclic‐monophosphor‐othioate (5,6‐DCl‐cBiMPS, 20 μM). The availability of I Na + was determined with test pulses to ± 0 mV every 3.5 seconds after 2.5‐second conditioning between ‐130 mV and‐50 mV and a holding potential at the resting potential of the cell under examination, and after wash‐in of either compound. The peak currents were fit to a Boltzmann equation, and expressed by the maximal attainable current INa + Na,max the mid‐point potential V½, and a steepness parameter a. Values are given by mean ± SEM. 8‐Br‐cAMP showed a significant shift of the availability curve in the hyperpolarized direction (V½= ‐82 ± 2 mV vs ‐ 66 ± 2 mV, n = 5, P < 0.05) with only minor changes of I + No,max and a. In contrast, 5,6‐DCI‐cBiMPS had no significant effect on V½ but increased I + Na,max by 8%± 2% versus control (n = 5. P < 0.05). In an intact muscle preparation we have found that 5,6‐DCI‐cBiMPS has a similar effect as that observed with the β‐adrenergic agonist ISO (100 nM), whereas 8‐Br‐cAMP exhibited a dissimilar action. This indicates, that ihe effects of ISO are transmitted by the cAMP system. On the other hand, 8‐Br‐cAMP, which is not as permeable and specific an activator of the cAMP dependent proteinkinase, may have other effects on the sodium channel, perhaps mediated through purinergic receptors.