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The mechanosensory activity generated by ventricular epicardial sensory neurites associated with afferent axons in thoracic sympathetic nerves was correlated with sensory field deformation (long axis, short axis, and transmural dimension changes), regional intramyocardial pressure, and ventricular chamber pressure in anesthetized dogs. Ventricular mechanosensory neurites generated activity that correlated best with strain developed along either the long or short axis of their epicardial sensory fields in most instances. Activity did not correlate normally to local wall thickness or to regional wall or chamber pressure development in most cases. During premature ventricular contractions, the activity generated by these sensory neurites correlated best with maximum strain developed along at least one sensory field epicardial vector. Identified sensory neurites were also activated by local application of the chemical bradykinin (10 microM) or by local ischemia. These data indicate that the activity generated by most ischemia-sensitive ventricular epicardial sensory neurites associated with afferent axons in sympathetic nerves is dependent on not only their local chemical milieu but on local mechanical deformation along at least one epicardial vector of their sensory fields.

Transmural heterogeneities of repolarizing currents underlie prominent differences in the electrophysiology and pharmacology of ventricular epicardial, endocardial, and M cells in a number of species. The degree to which heterogeneities exist between the right and left ventricles is not well appreciated. The present study uses standard microelectrode and whole cell patch-clamp techniques to contrast the electrophysiological characteristics and pharmacological responsiveness of tissues and myocytes isolated from right (RVE) and left canine ventricular epicardium (LVE). RVE and LVE studied under nearly identical conditions displayed major differences in the early repolarizing phases of the action potential. The magnitude of phase 1 in RVE was nearly threefold that in LVE: 28.7 +/- 6.2 vs. 10.6 +/- 4.1 mV (basic cycle length = 2,000 ms). Phase 1 in RVE was also more sensitive to alterations of the stimulation rate and to 4-aminopyridine (4-AP), suggesting a much greater contribution of the transient outward current (I(to) 1) in RVE than in LVE. The combination of 4-AP plus ryanodine, low chloride, or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (chloride channel blocker) completely eliminated the notch and all rate dependence of the early phases of the action potential, making RVE and LVE indistinguishable. At +70 mV, RVE myocytes displayed peak I(to) 1 densities between 28 and 37 pA/pF. LVE myocytes included cells with similar I(to) 1 densities (thought to represent subsurface cells) but also cells with much smaller current levels (thought to represent surface cells). Average peak I(to) 1 density was significantly smaller in LVE than in RVE at voltages more than or equal to +10 mV. Our data point to prominent differences in the magnitude of the I(to) 1-mediated action potential notch in cells at the surface of RVE compared with the LVE and suggest that important distinctions may exist in the response of these two tissues to pharmacological agents and pathophysiological states, as previously demonstrated for epicardium and endocardium. Our findings also suggest that a calcium-activated outward current contributes to the early repolarization phase in RVE and LVE and that the influence of this current, although small, is more important in the left ventricle.

We examined the responses of epicardial (Epi) and endocardial (Endo) layers to ATP-sensitive K+ (KATP) channel modulators during regional ischemia in anesthetized dogs. Five-minute occlusion of the left anterior descending coronary artery was repeated at 30-min interval. Monophasic action potentials (MAPs) and extracellular K+ concentrations ([K+]o) were measured at Epi and Endo layers. 5-Hydroxydecanoate (5-HD, 30 mg/kg iv), a KATP channel blocker, or nicorandil (NCR, 0.2-0.5 mg/kg iv), an opener, was administered before the third or fourth occlusion. Shortening rate of action potential duration at 90% repolarization (APD90) was greater at the Epi layer than at the Endo layer during the first 4 min after the second control occlusion (19.7 +/- 1.5 vs. 13.1 +/- 2.4%, n = 14, P < 0.05). 5-HD suppressed the shortening preferentially at the Epi layer and reduced the difference between the two layers (11.0 +/- 3.5 vs. 11.5 +/- 3.7%, n = 6, NS). In contrast, NCR augmented the shortening preferentially at the Epi layer and increased the difference between the two layers at 4 min (29.0 +/- 2.0 vs. 5.9 +/- 3.0%, n = 6, P < 0.05). The time differentiation of [K+]o rise was similar at the two layers during the control occlusion (0.44 vs. 0.50 mM/min, n = 12). 5-HD reduced the rate of [K+]o rise at both layers (0.34 vs. 0.40 mM/min), whereas NCR augmented the rate at the Epi layer (0.82 vs. 0.50 mM/min). Activation of KATP channels appears to be involved in ischemia-induced APD shortening and [K+]o rise. The different responses of the two layers suggest a lower threshold for activation and/or a denser distribution of KATP channels or other K+ channels at the Epi layer.

Ca2+ may play an important role in mesothelial cellular responses because Ca2+ acts as an intracellular messenger in a wide variety of cellular responses in different tissues. The present study was designed to clarify the mechanisms of cytosolic Ca2+ mobilization in the mesothelial cells. Rat pleural and pericardial mesothelial cells were maintained in vitro, and the Ca2+ movement was evaluated using fura 2. Histamine (30 microM to 10 mM) induced a biphasic elevation of intracellular levels of Ca2+ concentration ([Ca2+]i) that consisted of a rapid initial transient elevation followed by a sustained elevation. Neither removal of extracellular Ca2+ nor inhibition of Ca2+ influx by 1 microM nifedipine affected the histamine-induced initial transient elevation of [Ca2+]i in mesothelial cells. Nifedipine did not block histamine-induced sustained elevation of [Ca2+]i. KCl (25 and 50 mM) elicited a biphasic elevation of [Ca2+]i. However, this KCl-induced elevation of [Ca2+]i was abolished by nifedipine treatment. Ryanodine (10 microM) induced a transient elevation of [Ca2+]i in Ca(2+)-free solution. The histamine-induced elevation of [Ca2+]i was completely blocked by H1-receptor antagonists. These results suggest that the mesothelial cells have three pathways to increase [Ca2+]i: release from intracellular Ca2+ stores, Ca2+ influx through L-type voltage-dependent Ca2+ channels, and receptor-operated Ca2+ channels.