Conduction System Tutorial

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Gap Junctions (Cell-to-Cell Conduction)

In the heart, cardiac muscle cells (myocytes) are connected end to end by structures known as intercalated disks. These are irregular transverse thickenings of the sarcolemma, within which there are desmosomes that hold the cells together and to which the myofibrils are attached. Adjacent to the intercalated discs are the gap junctions, which allow action potentials to directly spread from one myocyte to the next. More specifically, the disks join the cells together by both mechanical attachment and protein channels. The firm mechanical connections are created between the adjacent cell membranes by proteins. The electrical connections (low resistance pathways, gap junctions) between the myocytes are via the channels formed by the protein connexin. These channels allow ion movements between cells (Figure 5). There are several different isoforms of connexins that can be identified within the various populations of myocytes (see below).

Figure 5. Shown are several cardiac myocytes in different states of excitation. The initial depolarization that occurred within the centrally located cell was induced via a pacemaker lead (fixated into the cell). This then resulted in the spread of depolarization of adjacent cells, in both directions, through cell-to-cell conduction via the gap junctions (nexus). Eventually all adjoining cells will depolarize. In other words, action potentials initiated in any of these cells will be conducted from cell to cell in either direction.

As noted above, not all cells elicit the same types of action potentials, even though excitation is propagated from cell to cell via their interconnections (gap junctions). Nevertheless, via gap junctions the slow response action potentials elicited in the sinoatrial nodal cells will trigger fast response action potentials in adjacent myocytes and then those within the remainder of the atria (Figure 6).

In a healthy heart, it takes approximately 30 msec for excitation to spread between the sinoatrial and atrioventricular nodes, and the widespread atrial activation occurs over a period of approximately 70 to 90 msec (Figures 2 and 3). The speed at which an action potential propagates through a given region of cardiac tissue can be described as the relative conduction velocity (Figure 2). The propogation velocity varies considerably within regions of the heart and is directly dependent on the relative diameter of given myocyte populations. For example, action potential conduction is greatly slowed as it passes through the atrioventricular node, but is rapid in the bundle branches connected via the His bundle. This nodal slowing is due to the: 1) small diameter of these cells; 2) tortuosity of the cellular pathway [3]; and 3) slower rates of rise of elicited action potentials. Nevertheless, this delay is essential to allow adequate time for ventricular filling.

Figure 6. Shown are the predominant conduction pathways in the heart and the relative time, in msec, that cells in these various regions become activated following an initial depolarization within the sinoatrial node. To the right are typical action potential waveforms that would be recorded from myocytes in these specific locations. The sinoatrial (SA) and atrioventricular (AV) nodal cells have similar shaped actions potentials. The nonpacemaker atrial cells elicit action potentials that have shapes somewhat between the slow response (nodal) and fast response cells (e.g., ventricular myocytes). The ventricular cells elicit fast response type action potentials, however their durations vary in length. Due to the rapid excitation within the Purkinje fiber system, the initiation of depolarization of the ventricular myocytes occurs within 30 to 40 msec, and is recorded as the QRS complex in the electrocardiogram.

Action potentials in the Purkinje fibers are of the fast response type (Figure 4), i.e., rapid depolarization rates that, in part, are due to their large diameters. This feature allows the Purkinje system to transfer depolarization to the majority of cells in the ventricular myocardium nearly in unison. It is important to note that the ventricular cells that are last to depolarize (those near the base of the heart) have shorter duration action potentials (shorter Ca2+ current), and thus are typically the ones to repolarize first. The ventricular myocardium repolarizes within the time period represented by the T-wave in the electrocardiogram, thus a change in the duration of this wave indicates a change in the duration of functional repolarization of the ventricular cells.