g through the Bainbridge effect 3 : the stretch-induced

g. through the Bainbridge effect 3 : the stretch-induced

increase Tyrphostin AG-1478 153436-53-4 in spontaneous pacemaker rate) of the heart. These mechano-electric feedback (MEF) responses are sustained in denervated (e.g. isolated 4–6 or transplanted 7–9 ) hearts, in isolated tissue 10,11 and even single cells – in both cardiac myocytes 12–16 and non-myocytes. 17–19 Figure 1. Simplified diagram of cardiac electromechanical integration. Cardiac electrophysiology controls cardiac mechanics via excitation-contraction coupling. Changes in the heart’s mechanical environment from contraction or external interventions affect electrophysiology … Adaptation to a highly dynamic mechanical environment is a crucial feature of normal cardiac function. It is involved in the regulation of beat-by-beat physiology, 4,20,21 and implicated in the progression of cardiac diseases, including rhythm disturbances. 22–25 For a compendium

of current insight into cardiac mechano-electric coupling and arrhythmias, from pipette to patient, see 26 . Although the mechanisms underlying cardiac mechanotransduction are not completely understood, key players are thought to include mechanosensitive ion channels (MSC). MSC are defined in the broadest sense by their ability to change ion channel open probability in response to mechanical stimuli, thereby converting mechanical

energy into the modification of an electrochemical signal. 27 MSC have been demonstrated to act as functional mechanotransducers in a number of different tissues, including the heart, and their block is capable of preventing or terminating certain mechanically-induced arrhythmias. 28,29 MSC can be subcategorised by the type of mechanical stimulation required for channel activation. Although these boundaries Carfilzomib are far from clear-cut, it is useful to make this conceptual distinction. In this review we shall focus on stretch-activated ion channels (SAC), which are those MSC whose switching from ‘closed’ to ‘open’ state can be driven over their full dynamic range by stretch alone, for example through direct mechanical membrane deformation (Figure 2). Figure 2. SAC current recording (top) and patch pipette suction (middle) used for membrane deformation (bottom). Using the patch clamp technique, the most common way to cause mechanical stimuli is to apply negative pressure to the inside of the pipette; this induces …

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