Chronotropy

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As Chronotropie (from ancient Greek χρόνος chronos "time" and τρόπος tropos "turning direction") is defined as the action on the action potential frequency in the sinus node and thus the impact frequency of the heart . The pacemaker function of the sinus node is based on a spontaneous depolarization of the heart muscle cells there ; the responsible current I f is carried by HCN channels and is an essential point of attack for chronotropy.

The natural frequency of the sinus node is 60–80 / min; the autonomic nervous system acts on it via the sympathetic (frequency-increasing, positive chronotropic) and parasympathetic (frequency-lowering, negative chronotropic) nervous system .

Positive chronotropy

The binding of catecholamines ( noradrenaline from local sympathetic varicosities as well as noradrenaline and adrenaline from the adrenal medulla ) to β 1 -adrenoceptors activates the signal chain

G-protein coupled receptor → activated G α →  adenylyl cyclase →  cAMP .

The cAMP attaches to unspecific cation channels from the class of HCN channels and increases their open probability. The increased inward current of sodium accelerates the spontaneous depolarization of the sinus node cells, so that the threshold potential is reached earlier, which results in a higher frequency.

Positive chronotropic drugs

Negative chronotropy

In addition, the heart is parasympathetically innervated by the vagus nerve , whose endings release acetylcholine , which binds to muscarinic acetylcholine receptors of subtype M 2 . This results in two negative chronotropic mechanisms:

  1. Activation of an inhibitory G protein so that the positive chronotropic signal path described above is inhibited,
  2. Opening of a potassium channel , the current I Kach of which counteracts the depolarization, through interaction with the βγ subunit .

Negative chronotropic drugs