Chronotropic

As chronotropy (from ancient Greek chronos χρόνος. Τρόπος time and tropos: turn direction ) refers to the effect on the frequency of action potentials in the pacemaker ( = sinus node ) and thus on the beat rate of the heart. The frequency of the pulse formation in the pacemaker cells is essentially dependent on the speed of Spontandepolarisation.

• 2.1 drugs with negative chronotropic effect

Positive chronotropy

Positive chronotropic effect ( increase in frequency ) by the sympathetic nervous system: norepinephrine ( from the Herzsympatikusfasern ) and adrenaline ( from the plasma ) bind to the β1 - adrenoceptor in the heart and activate a G- protein stimulating adenylyl cyclase. This results from the increased formation of cAMP to the activation of protein kinase A. This in turn phosphorylates the Ca2 channels of the cell membrane, thus leading to the opening of these channels (better: to increase the open probability ). Under noradrenaline / adrenaline effect thus flows more Ca2 into the cell, which ( the intracellular Ca2 storage ) leads to an additional release of intracellular Ca2 from the sarcoplasmic reticulum. Thus, the depolarization of the cell is accelerated (positive chronotropic effect).

In addition, cAMP added onto so-called HCN channels and thus increases their activity. Through these HCN channels, which make a significant contribution to Spontandepolarisation the sinus node cells, Na ions are now transported more rapidly into the cell, resulting in a more rapid depolarization, which in turn increases the heart rate.

Further effects of the sympathetic nervous system (both are also increased due to increased Ca2 influx ):

• Increasing the force of contraction of the heart ( positive inotropic effect )
• Faster reconciliation on atrioventricular conduction and thus faster (positive dromotropic effect )

Drugs with positive chronotropic effect

• Orciprenaline
• Adrenaline
• Theophylline
• Atropine

Negative chronotropy

Negative chronotropic effect ( drop in rate ) by the parasympathetic nervous system: a transmitter substance here is the acetylcholine with the muscarinic ( M ) acetylcholine receptors ( G protein- coupled ) reacts in the pacemaker cells ( M2 subtype ), and the opening of potassium channels effect, leading to a slowing of diastolic depolarization and thus a decrease in the heart rate.

Drugs with negative chronotropic effect

• Beta blocker
• Cardiac glycosides
• Certain types of calcium antagonists
• Ivabradine