Electrophysiological responses of cardiac muscle to isoproterenol covalently linked to glass beads.

We investigated the effects of isoproterenol aryl glass beads on the electrical properties of cardiac muscle and related these to our previous results concerning biochemical and contractile effects (Ingebretsen et al., Circ, Rs., 40: 474-484, 1977). Beads (10-15) were placed near one end to guinea pig papillary muscles mounted horizontally in a bath perfused with Krebs-Henseleit solution at 30 degrees C and stimulated at 0.2 Hz. The beads produced increased tension and elevation and slight lengthening of the plateau potential when [k+]o = 3.8 mM. After depolarization to a resting potential of -49 mV with [K+]o = 22 mM, isoproterenol beads restored contraction to a comparable extent as occurred with 10(-8) M soluble drug. During field stimulation, action potentials were initiated at the site of bead application and spread decrementally. When beads were placed distal to the site of point stimulation, virtually no excitation could be obtained from cells in the vicinity of the beads. When they were placed close to the stimulating electrode, the beads increased excitability and typical slow action potentials spread to the other end of the muscle. These potentials had the characteristics associated with the slow inward Ca2+ current. The slow channel blocker, D-600, blocked responses to isoproterenol beads. Tetrodotoxin caused responses similar to those obtained with K+ depolarization. The beads probably act by stimulating only a small fraction of the papillary muscle catecholamine receptors. Spread of action potentials from these sites and propagated tension depend on Ca2+ influx, but the nature of an intermediate messenger involved in the propagation of contractions is unknown.