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Nevertheless, the sinoatrial tissue of crucian carp heart is under a strong inhibitory cholinergic control in summer and in winter.

The sinoatrial tissue of the crucian carp heart is totally insensitive to beta-adrenergic stimulation lacking both inotropic and chronotropic effects.

Ventricular muscle of the crucian carp heart is also fairly insensitive to beta-adrenergic activation, as adrenaline and Iso cause about a modest 10%and40%0% increase in the force of contraction, respectively [ 37].

The absence of beta-adrenergic response in sinoatrial tissue of the crucian carp heart is probably due to maximal or near maximal activation of the molecular machinery involved in beta-adrenergic signaling pathway, in particular the L-type Ca2+ channels, under basal conditions.

Obviously, seasonal acclimatization of the crucian carp heart is mainly dependent on intrinsic molecular adjustments within individual cardiac myocytes [ 3, 9, 24, 25], while sensitivity to extrinsic modulation of cardiac function by the autonomic nervous system remain unaltered throughout the year.

Sinoatrial preparations of the crucian carp heart were almost totally insensitive to the nonselective beta-adrenergic agonist Iso.

Collectively these findings indicate that contribution of the endocardial NOS to cholinergic responses of the vertebrate heart is species and tissue dependent, and suggest that crucian carp belong to the group which is independent of NOS signaling.

Collectively the present findings indicate that responsiveness of the crucian carp heart to extrinsic autonomic modulation is similar in summer and winter acclimatized fish.

Therefore, upregulation of CARP, FHL2, and SQSTM1 in dKO hearts are primarily caused by post-transcriptional mechanisms.

Sinoatrial tissue of the crucian carp heart lacks positive chronotropic and inotropic responses to autonomic nervous agonists and contractility can be only down-regulated through activation of the muscarinic cholinergic receptors.

The present experiments indicate two major findings on autonomic nervous regulation of the crucian carp heart.