Modal gating behaviour of single sodium channels from the guinea-pig heart

A patch clamp method was used to study single Na channels on isolated ventricular cells from the guinea-pig heart. The normal gating behaviour of Na channels is characterized by short openings at the very beginning of the depolarizing pulse. The short openings (mean open time tau o is voltage independent, tau o = 0.39 +/- 0.11 ms, 6 patches, mean +S.E.M.) and also the blank sweeps (nulls) show a significant clustering. Long openings or long lasting bursts of openings were only exceptionally observed. The cardiotonic compound DPI 201-106 induced a clustering of long openings but with a voltage-dependent mean open time, short openings and nulls. Also in excised patches Na channels with long openings were observed showing a voltage-dependent mean open time. The different types of openings are reflected by a biexponential distribution of the open times in both DPI-modified- and excised-patch channels. It is proved that 1. the kinetic schemes within the same sample are distinctly different, 2. the different types of openings nonrandomly appear in clusters, 3. pharmacologicals tools (e.g. DPI) can induce a shift between the different kinetic schemes. The results indicate a modal gating behaviour of cardiac Na channels.